Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C47H55ClF3N5O6S3.2ClH |
Molecular Weight | 1047.535 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.CC1(C)CCC(=C(CN2CCN(CC2)C3=CC=C(C=C3)C(=O)NS(=O)(=O)C4=CC(=C(N[C@H](CCN5CCOCC5)CSC6=CC=CC=C6)C=C4)S(=O)(=O)C(F)(F)F)C1)C7=CC=C(Cl)C=C7
InChI
InChIKey=WDVGRPCSLPVWKC-VROLVAQFSA-N
InChI=1S/C47H55ClF3N5O6S3.2ClH/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);2*1H/t38-;;/m1../s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/18451170 | http://adisinsight.springer.com/drugs/800025430Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18806758
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18451170 | http://adisinsight.springer.com/drugs/800025430
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18806758
Navitoclax (ABT-263) is an oral selective inhibitor of B-cell leukemia 2 (Bcl-2) family of proteins with potential antineoplastic activity. Navitoclax is a small molecular with the formula of C47H55ClF3N5O6S3 and Molecular Weight of 974. As a Bad-like Bh3 minetic, ABT-263 binds to Bcl-2 family proteins Bcl-2, Bcl-xl and Bcl-w, disrupts the interaction between Bcl-2/Bcl-xl /Bcl-w and pro-apoptotic proteins such as Bim, Bad and Bak, which trigger the caspases-initiated cell death pathway to induce apoptosis. Navitoclax has been in phase II clinical trials by Abbvie for the treatment of prostate cancer, chronic lymphocytic leukaemia and lymphoma. However, this research has been discontinued.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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3.3 nM [IC50] | |||
Target ID: CHEMBL4860 |
1.0 nM [Ki] | ||
Target ID: CHEMBL4677 |
1.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse events |
---|---|---|
150 mg 1 times / day multiple, oral (starting) RP2D Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: |
unhealthy n = 15 Health Status: unhealthy Condition: Follicular lymphoma Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: |
Disc. AE: Increased white blood cell count, Increased white blood cell count... AEs leading to discontinuation/dose reduction: Increased white blood cell count (serious, 2 patients) Sources: Increased white blood cell count (serious, 2 patients) Bacterial sepsis (serious, 2 patients) Bacterial sepsis (serious, 2 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Bacterial sepsis | serious, 2 patients Disc. AE |
150 mg 1 times / day multiple, oral (starting) RP2D Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: |
unhealthy n = 15 Health Status: unhealthy Condition: Follicular lymphoma Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: |
Bacterial sepsis | serious, 2 patients Disc. AE |
150 mg 1 times / day multiple, oral (starting) RP2D Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: |
unhealthy n = 15 Health Status: unhealthy Condition: Follicular lymphoma Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: |
Increased white blood cell count | serious, 2 patients Disc. AE |
150 mg 1 times / day multiple, oral (starting) RP2D Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: |
unhealthy n = 15 Health Status: unhealthy Condition: Follicular lymphoma Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: |
Increased white blood cell count | serious, 2 patients Disc. AE |
150 mg 1 times / day multiple, oral (starting) RP2D Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: |
unhealthy n = 15 Health Status: unhealthy Condition: Follicular lymphoma Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00406809
Oral solution and tablets
Phase 2a dosing under 21 day continuous dosing.
150 mg lead-in dose for 7-14 days followed by a 325 mg continuous once daily dose.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18519752
A wide range of cellular activity is observed with Navitoclax (ABT-263) having a 50% growth inhibition (EC50) of 110 nM against the most sensitive line (H146), whereas its activity in the least sensitive line (H82) results in an EC50 at 22 uM.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
257408
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FDA ORPHAN DRUG |
251307
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FDA ORPHAN DRUG |
249107
Created by
admin on Fri Dec 15 19:39:26 GMT 2023 , Edited by admin on Fri Dec 15 19:39:26 GMT 2023
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CHEMBL443684
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DTXSID90148920
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C170202
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46937443
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W8FZ00AY2S
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300000001221
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1093851-28-5
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WW-99
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admin on Fri Dec 15 19:39:26 GMT 2023 , Edited by admin on Fri Dec 15 19:39:26 GMT 2023
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ACTIVE MOIETY
SUBSTANCE RECORD