Drug Details

General Information of the Drug (ID: DR6516)
Name
Temozolomide
Synonyms
Methazolastone; Temodal; Temodar; Temozolamide; Temozolodida; Temozolomidum; Essex brand of temozolomide; Scheringbrand of temozolomide; Temozolodida [Spanish]; Temozolomidum [Latin]; M B 39831; MB 39831; Sch 52365; M & B 39831; M&B 39831; M-39831; Sch-52365; Schering-Plough brand of temozolomide; TMZ-Bioshuttle; Temodal (TN); Temodar (TN); Temozolomide [INN:BAN]; M&B-39831; Temozolomide (JAN/USAN/INN); 3,4-Dihydro-3-methyl-4-oxoimidazo(5,1-d)-1,2,3,5-tetrazine-8-carboxamide; 3,4-Dihydro-3-methyl-4-oxoimidazo(5,1-d)-as-tetrazine-8-carboxamide; 3-Methyl-4-oxo-3,4-dihydroimidazo(5,1-d)(1,2,3,5)tetrazine-8-carboxamide; 3-Methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetraazine-8-carboxamide; 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide; 3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide; 8-Carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one; TMZ
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Molecular Type
Small molecule
Disease Brain cancer [ICD-11: 2A00] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 23.4 mgh/L
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 7.5 mg/L
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1 h
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability
Bioavailability
96% of drug becomes completely available to its intended biological destination(s)
Clearance
The drug present in the plasma can be removed from the body at the rate of 3.6 mL/min/kg
Elimination
Roughly 38% of administered temozolomide can be recovered over seven days, with 38% in the urine and only 0.8% in the feces
Half-life
The concentration or amount of drug in body reduced by one-half in 1.8 hours
Metabolism
The drug is metabolized via the nonenzymatic chemical conversion to the active metabolite
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 25.4585 micromolar/kg/day
Vd
The volume of distribution (Vd) of drug is 0.4 L/kg
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Formula
C6H6N6O2
PubChem CID
5394
Canonical SMILES
CN1C(=O)N2C=NC(=C2N=N1)C(=O)N
InChI
1S/C6H6N6O2/c1-11-6(14)12-2-8-3(4(7)13)5(12)9-10-11/h2H,1H3,(H2,7,13)
InChIKey
BPEGJWRSRHCHSN-UHFFFAOYSA-N
CAS Number
CAS 85622-93-1
GDSC
Temozolomide
TTD Drug ID
D0C8EU
DrugBank ID
DB00853
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Beta asarone      Acorus tatarinowii     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
                    In-vitro Model U-251MG CVCL_0021 Astrocytoma Homo sapiens
                    Experimental
                    Result(s)		 Beta-asarone could promote the entry of TMZ into U252 cells through the membrane.
          Biochanin A      Dalbergia volubilis     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation TP53  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
T98G CVCL_0556 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Biochanin A significantly enhanced the anticancer efficacy of temozolomide in GBM cells.
          Borneol      Chrysanthemum x morifolium     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Phosphorylation ATM  Molecule Info 
Pathway MAP
Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
Up-regulation Activity CASP7  Molecule Info 
Pathway MAP
Up-regulation Activity CASP9  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation FRP1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation TP53  Molecule Info 
Pathway MAP
                    In-vitro Model U-251MG CVCL_0021 Astrocytoma Homo sapiens
                    In-vivo Model U251 cell suspension (1*109 cells) was inoculated in the armpit of 6-week-old Balb/c nude mice.
                    Experimental
                    Result(s)		 Natural borneol enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage.
          Carnosic acid      Salvia rosmarinus     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
                    In-vitro Model U-251MG CVCL_0021 Astrocytoma Homo sapiens
LN-229 CVCL_0393 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma.
          Celastrol      Celastrus strigillosus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation NFKBIA  Molecule Info 
Pathway MAP
Up-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model SK-MEL-19 CVCL_6025 Cutaneous melanoma Homo sapiens
SK-MEL-100 CVCL_6067 Cutaneous melanoma Homo sapiens
SK-MEL-173 CVCL_6090 Melanoma Homo sapiens
SK-MEL-192 CVCL_6101 Melanoma Homo sapiens
                    Experimental
                    Result(s)		 Celastrol synergistically enhances temozolomide cytotoxicity in melanoma cells. Celastrol treatment increased the levels of ubiquitinated proteins, reduced the levels of tumor necrosis factor-alpha-induced IkappaB phosphorylation, and blocked NF-kappaB translocation to the nucleus.
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction ROS generation
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling.
          Delta-9-tetrahydrocannabinol      Cannabis sativa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
T98G CVCL_0556 Glioblastoma Homo sapiens
HG19 cells isolated from brain tumor biopsies Brain tumor Homo sapiens
                    In-vivo Model Tumors were induced in nude mice by subcutaneous injection of 5 * 106 U87 cells or 10 *106 T98 cells in PBS supplemented with 0.1% glucose.
                    Experimental
                    Result(s)		 The combined administration of Delta(9)-Tetrahydrocannabinol and temozolomide exerts a strong antitumoral action in glioma xenografts, an effect that is also observed in tumors that are resistant to TMZ treatment.
          Elemene      Pogostemon cablin     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ATM  Molecule Info 
Pathway MAP
Down-regulation Expression ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression H2AFX  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
T98G CVCL_0556 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
LN-229 CVCL_0393 Glioblastoma Homo sapiens
C6 CVCL_0194 Rat malignant glioma Rattus norvegicus
                    Experimental
                    Result(s)		 Beta-elemene enhances both radiosensitivity and chemosensitivity of glioblastoma cells through the inhibition of the ATM signaling pathway.
          Ellagic acid      Lagerstroemia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CDH1  Molecule Info 
Pathway MAP
Down-regulation Expression CDH2  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model C6 CVCL_0194 Rat malignant glioma Rattus norvegicus
                    Experimental
                    Result(s)		 Combining ellagic acid with temozolomide mediates the cadherin switch and angiogenesis in a glioblastoma model.
          Epigallocatechin gallate      Hamamelis virginiana     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression HSPA5  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
LN-229 CVCL_0393 Glioblastoma Homo sapiens
                    In-vivo Model 2*105 cells (U87 and U251) in a volume of 10L were injected into the right frontal lobe of the brain and thereafter the skin incision was sutured with silk thread in athymic mice.
                    Experimental
                    Result(s)		 Green tea epigallocatechin gallate enhances therapeutic efficacy of temozolomide in orthotopic mouse glioblastoma models.
          Honokiol      Magnolia officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
GL261 CVCL_Y003 Mouse glioblastoma Mus musculus
                    Experimental
                    Result(s)		 Honokiol enhanced temozolomide-induced autophagy and apoptosis in drug-sensitive and -tolerant glioma cells.
          Monocyte activating polypeptide II      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
                    In-vivo Model Mice were implanted subcutaneously with GSCs or GSCs stably transfected with pre-miR-590-3p into the right flank regions of mice at 2 * 106 cells density.
                    Experimental
                    Result(s)		 EMAP-II in combination with TMZ suppresse malignant biological behaviors of GSCs via miR-590-3p/MACC1 inhibiting PI3K/AKT/mTOR signaling pathway, and might provide potential therapeutic approaches for human GSCs.
          Noscapine      Papaver somniferum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model U87/DK CVCL_3428 Glioblastoma Homo sapiens
                    In-vivo Model For a xenograft model, 4*106 U87MG cells were inoculated subcutaneously into one flank of 5-6 weeks old, female nude mice.
                    Experimental
                    Result(s)		 NOS synergistically potentiated the efficacy of FDA-approved anti-cancer drugs against human glioblastoma cells, thereby allowing them to be used at lower doses and hence minimizing their toxic side effects.
          Paclitaxel      Taxus brevifolia     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression SLC2A1  Molecule Info 
Pathway MAP
                    In-vitro Model U-251MG CVCL_0021 Astrocytoma Homo sapiens
LN-229 CVCL_0393 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 A combination of TMZ and Taxol exerted synergistic inhibitory effects on Taxol resistant glioma cells.
          Piperine      Piper nigrum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression CCNE1  Molecule Info 
Pathway MAP
Down-regulation Expression CDK2  Molecule Info 
Pathway MAP
Down-regulation Expression CDK4  Molecule Info 
Pathway MAP
Down-regulation Expression CDK6  Molecule Info 
Pathway MAP
                    In-vitro Model U-251MG CVCL_0021 Astrocytoma Homo sapiens
T98G CVCL_0556 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Piperine synergistically enhances the effect of temozolomide against temozolomide-resistant human glioma cell lines.
          Progesterone      Dioscorea alata     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
U-118MG CVCL_0633 Glioma Homo sapiens
                    Experimental
                    Result(s)		 PROG enhances the cytotoxic effects of TMZ in GBM cells and reduces its toxic side effects in healthy primary cells.
          Quercetin      Averrhoa carambola     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation TP53  Molecule Info 
Pathway MAP
                    In-vitro Model SK-MEL-28 CVCL_0526 Cutaneous melanoma Homo sapiens
SK-MEL-5 CVCL_0527 Cutaneous melanoma Homo sapiens
DB-1 Melanoma Homo sapiens
                    Experimental
                    Result(s)		 Qct can sensitize cells to TMZ and that the mechanisms of sensitization involve modulation of p53 family members.
          Resveratrol      Gnetum parvifolium     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression GFAP  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation PRKAA1  Molecule Info 
Pathway MAP
                    In-vitro Model SHG-44 CVCL_6728 Astrocytoma Homo sapiens
                    In-vivo Model SHG44 cells (5*105 cells per mouse) in 5 uL of Hanks' solution were injected intracranially into the right caudate nucleus of 6- to 8-week-old female nude mice.
                    Experimental
                    Result(s)		 Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway.
          Shikonin      Lithospermum erythrorhizon     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-2  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression SNAI2  Molecule Info 
Pathway MAP
Down-regulation Expression VIM  Molecule Info 
Pathway MAP
                    In-vitro Model U-118MG CVCL_0633 Glioma Homo sapiens
                    Experimental
                    Result(s)		 GBM-derived cells treated with a combination of SHK and TMZ showed decreases in their proliferation and migration capacities. These decreases were followed by the suppression of GMT through a reduction of beta3 integrin, MMP-2, MMP-9, Slug and vimentin expression via inactivation of PI3K/AKT signaling.
          Thymoquinone      Nigella sativa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [21]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BECN1  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 TQ enhanced the anti-cancer activity of TMZ by inhibition of autophagy at the transcriptional level and decreased the colony-forming ability and NO production of U87MG cell line.
          Triptolide      Tripterygium hypoglaucum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [22]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression RELA  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model GIC-1 Glioblastoma multiforme Homo sapiens
                    Experimental
                    Result(s)		 TPL sensitizes GICs to TMZ by synergistically enhancing apoptosis, which is likely resulting from the augmented repression of NF-KappaB signaling.
          Vitamin D      Saccharomyces cerevisiae     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [23]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BECN1  Molecule Info 
Pathway MAP
Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Down-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
                    In-vitro Model C6 CVCL_0194 Rat malignant glioma Rattus norvegicus
                    In-vivo Model To establish the rat glioblastoma model, each rat was anesthetized. Following disinfection and incision of the skin with a scalpel, a hole was drilled through the skull 2-mm lateral and 2-mm anterior to the bregma, on the right side of the skull.
                    Experimental
                    Result(s)		 Combined use of TMZ and VD exerts synergistic antitumor effects on rat models of glioblastoma and may represent an effective therapeutic strategy.
    β. A List of Natural Product(s) Able to Reverse the Resistance of This Drug
          Acteoside      Cistanche     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [24]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CD107a  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation p38 beta  Molecule Info 
Pathway MAP
                    In-vitro Model C6 CVCL_0194 Rat malignant glioma Rattus norvegicus
                    Experimental
                    Result(s)		 Acteoside has beneficial effects on TMZ based glioblastoma therapy.
          Cyclopamine      Veratrum californicum     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression Gli1  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of TMZ with micellarized Cyp is a promising strategy for exerting different functions of drugs for tumor treatment.
          Sulforaphane      Brassica oleracea     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression MGMT  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
U-373MG ATCC CVCL_2219 Astrocytoma Homo sapiens
T98G CVCL_0556 Glioblastoma Homo sapiens
                    In-vivo Model Nude mouse models were established with U373-R GBM cells inoculated subcutaneously into the right flanks of 4-6-week-old female mice.
                    Experimental
                    Result(s)		 SFN effectively inhibited activity of NF-KappaB signaling pathway and then reduced MGMT expression to reverse the chemo-resistance to TMZ in T98G, U87-R and U373-R cell lines.
          Ursolic acid      Potentilla indica     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [27]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression MGMT  Molecule Info 
Pathway MAP
                    In-vitro Model LN-229 CVCL_0393 Glioblastoma Homo sapiens
LN-18 CVCL_0392 Glioblastoma Homo sapiens
T98G CVCL_0556 Glioblastoma Homo sapiens
                    In-vivo Model LN18 cells (5*106/mouse) were subcutaneously injected into the left hind flank of each female BALB/c mouse.
                    Experimental
                    Result(s)		 Ursolic acid attenuates temozolomide resistance in glioblastoma cells by downregulating O(6)-methylguanine-DNA methyltransferase (MGMT) expression.
Target and Pathway
Target(s) Epidermal growth factor receptor (EGFR)  Molecule Info 
Gamma-Histone H2AX (H2AFX)  Molecule Info 
Human Deoxyribonucleic acid (hDNA)  Molecule Info  [28]
Hypoxia-inducible factor 1 alpha (HIF-1A)  Molecule Info 
Matrix metalloproteinase-9 (MMP-9)  Molecule Info 
Vascular endothelial growth factor A (VEGFA)  Molecule Info 
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7301).
Reference 2 Antioxidant and selective anticancer activities of two Euphorbia species in human acute myeloid leukemia. Biomed Pharmacother. 2017 Jun;90:375-385.
Reference 3 Combination of Biochanin A and Temozolomide Impairs Tumor Growth by Modulating Cell Metabolism in Glioblastoma Multiforme. Anticancer Res. 2019 Jan;39(1):57-66.
Reference 4 Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage. Onco Targets Ther. 2018 Sep 4;11:5429-5439.
Reference 5 Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma. J Neurooncol. 2019 Jan;141(2):277-288.
Reference 6 Celastrol synergistically enhances temozolomide cytotoxicity in melanoma cells. Mol Cancer Res. 2009 Dec;7(12):1946-53.
Reference 7 Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling. Oncol Rep. 2014 Oct;32(4):1610-6.
Reference 8 A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther. 2011 Jan;10(1):90-103.
Reference 9 Beta-elemene enhances both radiosensitivity and chemosensitivity of glioblastoma cells through the inhibition of the ATM signaling pathway. Oncol Rep. 2015 Aug;34(2):943-51.
Reference 10 Combining Ellagic Acid with Temozolomide Mediates the Cadherin Switch and Angiogenesis in a Glioblastoma Model. World Neurosurg. 2019 Dec;132:e178-e184.
Reference 11 Green tea epigallocatechin gallate enhances therapeutic efficacy of temozolomide in orthotopic mouse glioblastoma models. Cancer Lett. 2011 Mar 28;302(2):100-8.
Reference 12 Improved effects of honokiol on temozolomide-induced autophagy and apoptosis of drug-sensitive and -tolerant glioma cells. BMC Cancer. 2018 Apr 3;18(1):379.
Reference 13 Combination of Endothelial-Monocyte-Activating Polypeptide-II with Temozolomide Suppress Malignant Biological Behaviors of Human Glioblastoma Stem Cells via miR-590-3p/MACC1 Inhibiting PI3K/AKT/mTOR Signal Pathway. Front Mol Neurosci. 2017 Mar 13;10:68.
Reference 14 Synergistic suppression of noscapine and conventional chemotherapeutics on human glioblastoma cell growth. Acta Pharmacol Sin. 2013 Jul;34(7):930-8.
Reference 15 Combination of temozolomide and Taxol exerts a synergistic inhibitory effect on Taxol?resistant glioma cells via inhibition of glucose metabolism. Mol Med Rep. 2015 Nov;12(5):7705-11.
Reference 16 Piperine synergistically enhances the effect of temozolomide against temozolomide-resistant human glioma cell lines. Bioengineered. 2020 Dec;11(1):791-800.
Reference 17 Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide. Biochem Pharmacol. 2018 Nov;157:266-274.
Reference 18 Quercetin abrogates chemoresistance in melanoma cells by modulating deltaNp73. BMC Cancer. 2010 Jun 11;10:282.
Reference 19 Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway. CNS Neurosci Ther. 2012 Jul;18(7):536-46.
Reference 20 Dual treatment with shikonin and temozolomide reduces glioblastoma tumor growth, migration and glial-to-mesenchymal transition. Cell Oncol (Dordr). 2017 Jun;40(3):247-261.
Reference 21 Thymoquinone synergistically potentiates temozolomide cytotoxicity through the inhibition of autophagy in U87MG cell line. Iran J Basic Med Sci. 2016 Aug;19(8):890-898.
Reference 22 Triptolide synergistically enhances temozolomide-induced apoptosis and potentiates inhibition of NF-KappaB signaling in glioma initiating cells. Am J Chin Med. 2014;42(2):485-503.
Reference 23 Autophagy enhancement contributes to the synergistic effect of vitamin D in temozolomide-based glioblastoma chemotherapy. Exp Ther Med. 2016 Jun;11(6):2153-2162.
Reference 24 Synergistic anticancer effect of acteoside and temozolomide-based glioblastoma chemotherapy. Int J Mol Med. 2019 Mar;43(3):1478-1486.
Reference 25 Combination therapy with micellarized cyclopamine and temozolomide attenuate glioblastoma growth through Gli1 down-regulation. Oncotarget. 2017 Jun 27;8(26):42495-42509.
Reference 26 Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-KappaB-dependent pathway downregulating MGMT expression. Int J Oncol. 2016 Feb;48(2):559-68.
Reference 27 Ursolic acid attenuates temozolomide resistance in glioblastoma cells by downregulating O(6)-methylguanine-DNA methyltransferase (MGMT) expression. Am J Transl Res. 2016 Jul 15;8(7):3299-308.
Reference 28 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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