Natural Product (NP) Details

General Information of the NP (ID: NP6636)
Name
Daunorubicin
Synonyms
daunorubicin; Daunomycin; 20830-81-3; Cerubidine; Acetyladriamycin; Leukaemomycin C; Rubidomycin; (+)-Daunomycin; DaunoXome; Daunorubicinum; Daunorubicine; Cerubidin; Rubomycin C; RP 13057; C27H29NO10; NSC-82151; Daunarubicinum; Daunorrubicina; DaunoXome (TN); Daunamycin; FI 6339; UNII-ZS7284E0ZP; ZS7284E0ZP; (8S-cis)-8-Acetyl-10-((3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyrannosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-napthacenedione; CHEBI:41977; FI6339; FI-6339; NCGC00024246-05; Anthracyline; NDC-0082-4155; DSSTox_CID_2883; DSSTox_RID_76773; DSSTox_GSID_22883; RP-13057; Daunorubicinum [INN-Latin]; MLS000069508; Daunorubicin [INN:BAN]; RCRA waste no. U059; (1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranoside; CAS-20830-81-3; Daunorubicin (INN); NSC82151; SMR000058559; NDC 0082-4155; CCRIS 914; SR-01000000033; SR-05000001600; NSC-83142; HSDB 5095; NCI-C04693; EINECS 244-069-7; NSC 83142; VS-103; BRN 1445583; Tocris-1467; Daunorubicin(Daunomycin); AI3-52942; Prestwick3_000487; CHEMBL178; SCHEMBL3041; BSPBio_000353; 5,12-Naphthacenedione, 8-acetyl-10-((3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8S-cis)-; cid_62770; BPBio1_000389; GTPL7063; DTXSID7022883; BDBM32017; Valrubicin impurity, daunorubicin; HMS2089H04; HMS2091K06; Pharmakon1600-01500223; ZINC3917708; Tox21_110896; BDBM50368352; GR-318; HY-13062A; LMPK13050002; MFCD00866340; NSC756717; Tox21_110896_1; CCG-212559; CS-2004; DB00694; NSC-756717; NCGC00024246-06; NCGC00024246-07; NCGC00024246-09; NCGC00024246-10; NCGC00024246-15; NCGC00025173-01; (1S,3S)-3-acetyl-3,5,12-trihydroxy-10-(methyloxy)-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranoside; (1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-a-L-lyxo-hexopyranoside; (7S,9R)-9-Acetyl-7-[(2S,4S,5S,6S)-4-amino-5-hydroxy-6-methyl-oxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione; (7S,9S)-9-acetyl-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione; 5,12-Naphthacenedione, 8-acetyl-10-((3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8S,10S)-; SBI-0206677.P002; AB00514669; 30D813; C01907; D07776; Epirubicin hydrochloride impurity, daunorubicin-; 15159-EP2270008A1; 15159-EP2272827A1; 15159-EP2277565A2; 15159-EP2277566A2; 15159-EP2277567A1; 15159-EP2277568A2; 15159-EP2277569A2; 15159-EP2277570A2; 15159-EP2289892A1; 15159-EP2292280A1; 15159-EP2292617A1; 15159-EP2295416A2; 15159-EP2295426A1; 15159-EP2295427A1; 15159-EP2298748A2; 15159-EP2298778A1; 15159-EP2301928A1; 15159-EP2305642A2; 15159-EP2305679A1; 15159-EP2308833A2; 15159-EP2308861A1; 15159-EP2311808A1; 15159-EP2311829A1; 15159-EP2311842A2; 15159-EP2316832A1; 15159-EP2316833A1; 16803-EP2272832A1; 16803-EP2277565A2; 16803-EP2277566A2; 16803-EP2277567A1; 16803-EP2277568A2; 16803-EP2277569A2; 16803-EP2277570A2; 16803-EP2280012A2; 16803-EP2281815A1; 16803-EP2286812A1; 16803-EP2292280A1; 16803-EP2292615A1; 16803-EP2298768A1; 16803-EP2301928A1; 16803-EP2301933A1; 16803-EP2305640A2; 16803-EP2305671A1; 16803-EP2311825A1; 16803-EP2311827A1; 16803-EP2311840A1; 16803-EP2316937A1; AB00514669-09; AB01644616_09; AB01644616_10; Q411659; SR-01000000033-4; SR-05000001600-1; SR-05000001600-2; BRD-K43389675-001-01-3; BRD-K43389675-003-02-7; BRD-K43389675-003-03-5; BRD-K43389675-003-20-9; 2-HYDROXY-5-(4-NITRO-PHENYLSULFAMOYL)-BENZOICACID; (7S,9S)-7-[(2R,4S,5S,6S)-4-azanyl-6-methyl-5-oxidanyl-oxan-2-yl]oxy-9-ethanoyl-4-methoxy-6,9,11-tris(oxidanyl)-8,10-dihydro-7H-tetracene-5,12-dione;hydrochloride; (7S,9S)-9-acetyl-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-quinone;hydrochloride; (7S,9S)-9-acetyl-7-[[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyl-2-oxanyl]oxy]-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione;hydrochloride; (8S,10S)-8-acetyl-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione; (8S-cis)-8-Acetyl-10-[(3-amino-2,3,6-trideoxy-.alpha.-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro--6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione; 5,12-Naphthacenedione,8-acetyl-10-[(3-amino-2,3,6-trideoxy-a-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8S,10S)-
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Species Origin Streptomyces peucetius ...     Click to Show/Hide
Streptomyces peucetius
SuperKingdom: Bacteria
Phylum: Actinobacteria
Class: Actinomycetia
Order: Streptomycetales
Family: Streptomycetaceae
Genus: Streptomyces
Species: Streptomyces peucetius
Disease Acute myeloid leukemia [ICD-11: 2A60] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -6.702
 
MDCK Permeability
 -5.341
 
PAMPA
 +++
 
HIA
 +++
 
Distribution
VDss
 1.626
 
PPB
 97.6%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 ++
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 - - -
HLM Stability
 - - -
 
Excretion
CLplasma
 14.759
 
T1/2
 3.603
Toxicity
DILI
 +++
 
Rat Oral Acute Toxicity
 +++
 
FDAMDD
 +++
 
Respiratory
 +++
 
Human Hepatotoxicity
 +++
 
Ototoxicity
 +++
 
Drug-induced Nephrotoxicity
 +++
 
Drug-induced Neurotoxicity
 +
 
Hematotoxicity
 +++
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C27H29NO10
PubChem CID
30323
Canonical SMILES
CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)C)O)N)O
InChI
1S/C27H29NO10/c1-10-22(30)14(28)7-17(37-10)38-16-9-27(35,11(2)29)8-13-19(16)26(34)21-20(24(13)32)23(31)12-5-4-6-15(36-3)18(12)25(21)33/h4-6,10,14,16-17,22,30,32,34-35H,7-9,28H2,1-3H3/t10-,14-,16-,17-,22+,27-/m0/s1
InChIKey
STQGQHZAVUOBTE-VGBVRHCVSA-N
CAS Number
CAS 20830-81-3
ChEBI ID
CHEBI:41977
TTD Drug ID
D01XWG
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          NL-101      Anaplastic large cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 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		 Up-regulation Expression BAD  Molecule Info 
Pathway MAP
Up-regulation Expression BCL2L11  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP7  Molecule Info 
Pathway MAP
                    In-vitro Model MV4-11 CVCL_0064 Childhood acute monocytic leukemia Homo sapiens
MOLM-13 CVCL_2119 Adult acute myeloid leukemia Homo sapiens
THP-1 CVCL_0006 Childhood acute monocytic leukemia Homo sapiens
HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
Kasumi-1 CVCL_0589 Acute myeloid leukemia Homo sapiens
NOMO-1 CVCL_1609 Adult acute monocytic leukemia Homo sapiens
OCI-AML-2 CVCL_1619 Adult acute myeloid leukemia Homo sapiens
OCI-AML-3 CVCL_1844 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 NL 101 in combination with daunorubicin could be an alternative novel therapeutic strategy for treating leukemia.
          Oxaliplatin      Colorectal cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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 Expression TOP2A  Molecule Info 
Pathway MAP
                    In-vitro Model SK-OV-3 CVCL_0532 Ovarian serous cystadenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Composite micelles showed reduced systematic toxicity and greater synergistic effect than combination of small molecules of hydrophilic platinum drug Oxa(II) and hydrophobic drug DRB both in vitro and in vivo.
          Bortezomib      Mantle cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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 Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
                    In-vitro Model Jurkat CVCL_0065 T acute lymphoblastic leukemia Homo sapiens
MOLT-4 CVCL_0013 Adult T acute lymphoblastic leukemia Homo sapiens
Daudi CVCL_0008 EBV-related Burkitt lymphoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of bortezomib and daunorubicin significantly enhanced their apoptosis inducing effect in T ALL cells, which may warrant further investigation in preclinical and clinical investigations.
          SG611-PDCD5      Acute lymphoblastic leukemia     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    In-vitro Model KG-1a CVCL_1824 Adult acute myeloid leukemia Homo sapiens
MEG-01 CVCL_0425 Chronic myelogenous leukemia Homo sapiens
BV-173 CVCL_0181 Chronic myelogenous leukemia Homo sapiens
SUP-B15 CVCL_0103 B acute lymphoblastic leukemia Homo sapiens
K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
                    In-vivo Model The triple-regulated CRAd carrying SG611-PDCD5 and nude mouse xenograft models of K562 cells were constructed in this study.
                    Experimental
                    Result(s)		 Treatment with SG611-PDCD5 in combination with low-dose daunorubicin elicited more potent anti-proliferative and proapoptotic effects in leukemic cells in a dose-dependent manner.
          SG611-VSTM1      Acute lymphoblastic leukemia     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    In-vivo Model For a xenograft model, 1*109 human K562 cells were injected into the inguinal mammary fat pad of Balb/c congenic athymic nude mice.
                    Experimental
                    Result(s)		 An important role for VSTM1 in the pathogenesis of leukemia, and SG611-VSTM1 may be a promising agent for enhancing chemosensitivity in leukemia therapy.
          Glasdegib      Chronic myelomonocytic leukaemia     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    Experimental
                    Result(s)		 Glasdegib plus cytarabine/daunorubicin was well tolerated and associated with clinical activity in patients with untreated AML or high-risk MDS.
          Sunitinib      Malignant digestive organ neoplasm     Click to Show/Hide the Molecular Data of This Drug
                 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 MV4-11 CVCL_0064 Childhood acute monocytic leukemia Homo sapiens
Ba/F3 CVCL_0161 Healthy Mus musculus
MOLM-14 CVCL_7916 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 The addition of potent FLT3 inhibitors such as SU11248 to AML chemotherapy regimens could result in improved treatment results.
          Imatinib      Mantle cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Experimental
                    Result(s)		 The combination of IM with a standard "3+7" regiment was well tolerated and provided a high response rate.
    β. A List of Drug(s) Whose Adverse Effect can be Decreased by This NP
          PP242      Colon cancer     Click to Show/Hide the Molecular Data of This Drug
                 Decreasing Adverse Drug Reaction     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 Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model THP-1 CVCL_0006 Childhood acute monocytic leukemia Homo sapiens
SUP-B15 CVCL_0103 B acute lymphoblastic leukemia Homo sapiens
JeKo-1 CVCL_1865 Mantle cell lymphoma Homo sapiens
NB4 CVCL_0005 Acute promyelocytic leukemia Homo sapiens
                    Experimental
                    Result(s)		 PP242 effectively eliminated this deleterious side effect of DNR and synergistically enhanced the anticancer ability of DNR treatment. PP242, especially in combination with DNR, exerts significant antileukemia effects.
          Rapamycin      Multiple myeloma     Click to Show/Hide the Molecular Data of This Drug
                 Decreasing Adverse Drug Reaction     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
                    In-vitro Model SUP-B15 CVCL_0103 B acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 RAPA effectively eliminated this deleterious side effect of DNR, which might enhance DNR's ability to kill drug-resistant cancer.
          Olaparib      Ovarian cancer     Click to Show/Hide the Molecular Data of This Drug
                 Decreasing Adverse Drug Reaction     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
                    In-vitro Model KG-1a CVCL_1824 Adult acute myeloid leukemia Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Olaparib interferes with anthracycline metabolism, and suggest that this phenomenon might be utilized for combating anthracycline resistance.
Target and Pathway
Target(s) Human Deoxyribonucleic acid (hDNA)  Molecule Info  [13]
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: 7063).
Reference 2 Novel SAHA?bendamustine hybrid NL?101 in combination with daunorubicin synergistically suppresses acute myeloid leukemia. Oncol Rep. 2020 Jul;44(1):273-282.
Reference 3 Co-delivery of daunomycin and oxaliplatin by biodegradable polymers for safer and more efficacious combination therapy. J Control Release. 2012 Nov 10;163(3):304-14.
Reference 4 Combination of bortezomib and daunorubicin in the induction of apoptosis in T-cell acute lymphoblastic leukemia. Mol Med Rep. 2017 Jul;16(1):101-108.
Reference 5 Synergistic antitumoral efficacy of a novel replicative adenovirus SG611-PDCD5 and daunorubicin in human leukemic cells. Onco Targets Ther. 2018 Aug 23;11:5121-5132.
Reference 6 Synergistic antitumor activity of triple-regulated oncolytic adenovirus with VSTM1 and daunorubicin in leukemic cells. Apoptosis. 2016 Oct;21(10):1179-90.
Reference 7 Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310.
Reference 8 Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD-positive leukemic cells. Blood. 2004 Dec 15;104(13):4202-9.
Reference 9 The addition of daunorubicin to imatinib mesylate in combination with cytarabine improves the response rate and the survival of patients with myeloid blast crisis chronic myelogenous leukemia (AFR01 study). Leuk Res. 2011 Jun;35(6):777-82.
Reference 10 The antileukemia roles of PP242 alone or in combination with daunorubicin in acute leukemia. Anticancer Drugs. 2015 Apr;26(4):410-21.
Reference 11 Antileukaemia effect of rapamycin alone or in combination with daunorubicin on Ph+ acute lymphoblastic leukaemia cell line. Hematol Oncol. 2012 Sep;30(3):123-30.
Reference 12 Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3. Cancers (Basel). 2020 Oct 26;12(11):3127.
Reference 13 31P NMR spectra of ethidium, quinacrine, and daunomycin complexes with poly(adenylic acid).poly(uridylic acid) RNA duplex and calf thymus DNA. Biochemistry. 1989 Apr 4;28(7):2804-12.
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