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Details

Stereochemistry ABSOLUTE
Molecular Formula C47H55ClF3N5O6S3
Molecular Weight 974.613
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NAVITOCLAX

SMILES

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=JLYAXFNOILIKPP-KXQOOQHDSA-N
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

HIDE SMILES / InChI

Description

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.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
3.3 nM [IC50]
1.0 nM [Ki]
1.0 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown

Doses

AEs

PubMed

Sample Use Guides

In Vivo Use Guide
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
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.