Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMNE56X)

Drug Name
ABT-263 Drug Info
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
Indication
Disease Entry ICD 11 Status REF
Myelofibrosis 2A20.2 Phase 3 [1]
Relapsed or refractory chronic lymphocytic leukaemia 2A82.0 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 2 [3]
Cross-matching ID
PubChem CID
24978538
ChEBI ID
CHEBI:94128
CAS Number
CAS 923564-51-6
TTD Drug ID
DMNE56X
VARIDT Drug ID
DR01365
INTEDE Drug ID
DR1839

Molecule(s) Related to This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Apoptosis regulator Bcl-2 (BCL-2) TTJGNVC BCL2_HUMAN Inhibitor [4]
Apoptosis regulator Bcl-W (BCL-W) TTQ79W8 B2CL2_HUMAN Inhibitor [4]
Apoptosis regulator Bcl-xL (BCL-xL) TTU1E82 B2CL1_HUMAN Inhibitor [4]
G1/S-specific cyclin-D1 (CCND1) TTFCJ7S CCND1_HUMAN Inhibitor [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID Highest Status REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Phase 2 [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID Highest Status REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Phase 2 [7]

The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule Molecule Type Gene Name Liver Colon Kidney Small Intestine
Apoptosis regulator Bcl-xL (BCL-xL) DTT BCL2L1 4.863 5.664 6.092 5.843
Apoptosis regulator Bcl-W (BCL-W) DTT BCL2L2 6.358 7.838 7.493 7.567
Apoptosis regulator Bcl-2 (BCL-2) DTT BCL2 3.963 4.739 4.146 4.878
P-glycoprotein 1 (ABCB1) DTP P-GP 7.009 6.988 7.442 8.135
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 11.692 6.58 4.984 9.089
Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease Myelofibrosis
ICD Disease Classification 2A20.2
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Apoptosis regulator Bcl-2 (BCL-2) DTT BCL2 2.52E-02 0.17 0.72
P-glycoprotein 1 (ABCB1) DTP P-GP 1.08E-01 -2.87E-01 -5.57E-01
P-glycoprotein 1 (ABCB1) DTP P-GP 2.05E-01 1.60E-01 1.37E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 3.18E-03 2.30E-01 2.71E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 8.32E-01 4.74E-02 1.73E-01
Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1 ClinicalTrials.gov (NCT04472598) Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis (TRANSFORM-1). U.S. National Institutes of Health.
2 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).
3 Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.Nat Rev Drug Discov. 2016 Aug;15(8):533-50.
4 Clinical pipeline report, company report or official report of Roche (2009).
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 The B-cell lymphoma 2 (BCL2)-inhibitors, ABT-737 and ABT-263, are substrates for P-glycoprotein. Biochem Biophys Res Commun. 2011 May 6;408(2):344-9.
7 Effect of rifampin on the pharmacokinetics, safety and tolerability of navitoclax (ABT-263), a dual inhibitor of Bcl-2 and Bcl-XL , in patients with cancer. J Clin Pharm Ther. 2014 Dec;39(6):680-4.