Drug Details

General Information of the Drug (ID: DR7304)
Name
ABT-263
Synonyms
Navitoclax; ABT 263; S1001_Selleck; ABT263, Navitoclax; 4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-({(1R)-3-morpholin-4-yl-1-[(phenylsulfanyl)methyl]propyl}amino)-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide
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Molecular Type
Small molecule
Disease Chronic lymphocytic leukaemia [ICD-11: 2A82] Phase 2 [1]
Structure
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2D MOL

3D MOL

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Formula
C47H55ClF3N5O6S3
PubChem CID
24978538
Canonical SMILES
CC1(CCC(=C(C1)CN2CCN(CC2)C3=CC=C(C=C3)C(=O)NS(=O)(=O)C4=CC(=C(C=C4)NC(CCN5CCOCC5)CSC6=CC=CC=C6)S(=O)(=O)C(F)(F)F)C7=CC=C(C=C7)Cl)C
InChI
1S/C47H55ClF3N5O6S3/c1-46(2)20-18-42(34-8-12-37(48)13-9-34)36(31-46)32-55-22-24-56(25-23-55)39-14-10-35(11-15-39)45(57)53-65(60,61)41-16-17-43(44(30-41)64(58,59)47(49,50)51)52-38(19-21-54-26-28-62-29-27-54)33-63-40-6-4-3-5-7-40/h3-17,30,38,52H,18-29,31-33H2,1-2H3,(H,53,57)/t38-/m1/s1
InChIKey
JLYAXFNOILIKPP-KXQOOQHDSA-N
CAS Number
CAS 923564-51-6
GDSC
ABT-263
TTD Drug ID
D06ETI
DrugBank ID
DB12340
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Apigenin      Psilotum nudum     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 [2]
                    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 Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation FOXO3  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
NCI-H1650 CVCL_1483 Lung adenocarcinoma Homo sapiens
NCI-H3255 CVCL_6831 Lung adenocarcinoma Homo sapiens
SK-MEL-28 CVCL_0526 Cutaneous melanoma Homo sapiens
                    Experimental
                    Result(s)		 Apigenin upregulated the expression of Noxa in EGFRm tumor cells by targeting the AKT-FoxO3a pathway, thereby synergizing with ABT-263 to suppress tumor cell growth and proliferation in vitro and in vivo.
    β. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Wogonin      Scutellaria amoena     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     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 MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model ARAC-8C CVCL_GZ09 T acute lymphoblastic leukemia Homo sapiens
MOLT-4 CVCL_0013 Adult T acute lymphoblastic leukemia Homo sapiens
Jurkat CVCL_0065 T acute lymphoblastic leukemia Homo sapiens
KM-H2 CVCL_1330 Hodgkin lymphoma Homo sapiens
                    In-vivo Model Immunodeficient mice (Rag2-/-/II2rg-/-) were implanted subcutaneously in the dorsal flank region with CEM (5*107 cells).
                    Experimental
                    Result(s)		 Wogonin potentiates the lethality of ABT-263 in ABT-263-resistant cancer cells and wogonin reduces the effective dose of ABT-263 thereby possibly decreasing the risk of adverse side effects.
Target and Pathway
Target(s) Apoptosis regulator Bcl-2 (BCL-2)  Molecule Info  [4]
Apoptosis regulator Bcl-W (BCL-W)  Molecule Info  [4]
Apoptosis regulator Bcl-xL (BCL-xL)  Molecule Info  [4]
G1/S-specific cyclin-D1 (CCND1)  Molecule Info  [5]
KEGG Pathway MicroRNAs in cancer Click to Show/Hide
2 FoxO signaling pathway
3 Cell cycle
4 p53 signaling pathway
5 PI3K-Akt signaling pathway
6 AMPK signaling pathway
7 Wnt signaling pathway
8 Hippo signaling pathway
9 Focal adhesion
10 Jak-STAT signaling pathway
11 Prolactin signaling pathway
12 Thyroid hormone signaling pathway
13 Oxytocin signaling pathway
14 Hepatitis B
15 Measles
16 HTLV-I infection
17 Pathways in cancer
18 Viral carcinogenesis
19 Proteoglycans in cancer
20 Colorectal cancer
21 Pancreatic cancer
22 Endometrial cancer
23 Glioma
24 Prostate cancer
25 Thyroid cancer
26 Melanoma
27 Bladder cancer
28 Chronic myeloid leukemia
29 Acute myeloid leukemia
30 Small cell lung cancer
31 Non-small cell lung cancer
32 Viral myocarditis
33 NF-kappa B signaling pathway
34 HIF-1 signaling pathway
35 Sphingolipid signaling pathway
36 Protein processing in endoplasmic reticulum
37 Apoptosis
38 Adrenergic signaling in cardiomyocytes
39 Neurotrophin signaling pathway
40 Cholinergic synapse
41 Amyotrophic lateral sclerosis (ALS)
42 Toxoplasmosis
43 Tuberculosis
44 Epstein-Barr virus infection
45 Ras signaling pathway
46 Transcriptional misregulation in cancer
NetPath Pathway TCR Signaling Pathway Click to Show/Hide
2 IL2 Signaling Pathway
3 EGFR1 Signaling Pathway
4 TGF_beta_Receptor Signaling Pathway
5 Notch Signaling Pathway
6 Wnt Signaling Pathway
7 IL5 Signaling Pathway
8 IL3 Signaling Pathway
9 Leptin Signaling Pathway
10 RANKL Signaling Pathway
11 TSLP Signaling Pathway
Panther Pathway Apoptosis signaling pathway Click to Show/Hide
2 PI3 kinase pathway
3 Wnt signaling pathway
4 CCKR signaling map ST
5 Oxidative stress response
Pathway Interaction Database Direct p53 effectors Click to Show/Hide
2 Notch signaling pathway
3 Coregulation of Androgen receptor activity
4 Validated transcriptional targets of AP1 family members Fra1 and Fra2
5 Presenilin action in Notch and Wnt signaling
6 Integrin-linked kinase signaling
7 Regulation of Telomerase
8 E-cadherin signaling in the nascent adherens junction
9 ATF-2 transcription factor network
10 AP-1 transcription factor network
11 FOXM1 transcription factor network
12 Neurotrophic factor-mediated Trk receptor signaling
13 C-MYB transcription factor network
14 Validated nuclear estrogen receptor alpha network
15 Signaling mediated by p38-gamma and p38-delta
16 Regulation of nuclear beta catenin signaling and target gene transcription
17 Validated targets of C-MYC transcriptional repression
18 Trk receptor signaling mediated by PI3K and PLC-gamma
19 Regulation of retinoblastoma protein
20 Signaling events mediated by focal adhesion kinase
21 Role of Calcineurin-dependent NFAT signaling in lymphocytes
22 IL2-mediated signaling events
23 IL2 signaling events mediated by PI3K
24 Ceramide signaling pathway
25 RXR and RAR heterodimerization with other nuclear receptor
26 HIV-1 Nef: Negative effector of Fas and TNF-alpha
27 Caspase Cascade in Apoptosis
28 Signaling events mediated by Stem cell factor receptor (c-Kit)
29 EPO signaling pathway
30 IL2 signaling events mediated by STAT5
31 IL3-mediated signaling events
Reactome Pre-NOTCH Transcription and Translation Click to Show/Hide
2 RMTs methylate histone arginines
3 Ubiquitin-dependent degradation of Cyclin D1
4 Cyclin D associated events in G1
5 Activation of BAD and translocation to mitochondria
6 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
7 The NLRP1 inflammasome
WikiPathways Apoptosis Click to Show/Hide
2 Apoptosis Modulation and Signaling
3 DNA Damage Response (only ATM dependent)
4 DNA Damage Response
5 Notch Signaling Pathway
6 G1 to S cell cycle control
7 Wnt Signaling Pathway and Pluripotency
8 TGF beta Signaling Pathway
9 Wnt Signaling Pathway Netpath
10 Copper homeostasis
11 Focal Adhesion
12 PPAR Alpha Pathway
13 Mesodermal Commitment Pathway
14 Hair Follicle Development: Organogenesis (Part 2 of 3)
15 Bladder Cancer
16 Pre-NOTCH Expression and Processing
17 S Phase
18 Polycystic Kidney Disease Pathway
19 Retinoblastoma (RB) in Cancer
20 Spinal Cord Injury
21 Integrated Pancreatic Cancer Pathway
22 Prostate Cancer
23 Signaling Pathways in Glioblastoma
24 IL-7 Signaling Pathway
25 Leptin signaling pathway
26 miR-targeted genes in muscle cell - TarBase
27 miR-targeted genes in lymphocytes - TarBase
28 miR-targeted genes in epithelium - TarBase
29 Integrated Breast Cancer Pathway
30 miRNAs involved in DNA damage response
31 miRNA Regulation of DNA Damage Response
32 Androgen receptor signaling pathway
33 Senescence and Autophagy in Cancer
34 IL-2 Signaling Pathway
35 FAS pathway and Stress induction of HSP regulation
36 Kit receptor signaling pathway
37 IL-3 Signaling Pathway
38 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
39 Nanoparticle triggered autophagic cell death
40 Amyotrophic lateral sclerosis (ALS)
41 Corticotropin-releasing hormone
42 Interleukin-11 Signaling Pathway
43 miR-targeted genes in leukocytes - TarBase
44 Integrated Cancer pathway
45 Intrinsic Pathway for Apoptosis
46 TP53 Network
47 Influenza A virus infection
48 IL-5 Signaling Pathway
49 IL-6 signaling pathway
50 TNF alpha Signaling Pathway
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: 8319).
Reference 2 BH3 mimetic ABT-263 enhances the anticancer effects of apigenin in tumor cells with activating EGFR mutation. Cell Biosci. 2019 Jul 23;9:60.
Reference 3 Targeting CDK9 by wogonin and related natural flavones potentiates the anti-cancer efficacy of the Bcl-2 family inhibitor ABT-263. Int J Cancer. 2015 Feb 1;136(3):688-98.
Reference 4 Clinical pipeline report, company report or official report of Roche (2009).
Reference 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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