MedKoo Cat#: 201970 Name: Navitoclax (ABT-263) CAS#: 923564-51-6 Chemical Formula: C47H55ClF3N5O6S3 Exact Mass: 973.29551 Molecular Weight: 974.61 Elemental Analysis: C, 57.92; H, 5.69; Cl, 3.64; F, 5.85; N, 7.19; O, 9.85; S, 9.87

Synonym: ABT 263; ABT-263; ABT263; Navitoclax

IUPAC/Chemical Name: (R)-4-(4-((4-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-morpholino-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide

InChi Key: JLYAXFNOILIKPP-KXQOOQHDSA-N

InChi Code: 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/h4-17,30,38,52H,18-29,31-33H2,1-2H3,(H,53,57)/t38-/m1/s1

SMILES Code: O=C(NS(=O)(C1=CC=C(N[C@H](CCN2CCOCC2)CSC3=CC=CC=C3)C(S(=O)(C(F)(F)F)=O)=C1)=O)C4=CC=C(N5CCN(CC6=C(C7=CC=C(Cl)C=C7)CCC(C)(C)C6)CC5)C=C4

Technical Data

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Certificate of Analysis: View CoA: current batch, Lot#BBC60830

QC Data: View QC data: current batch, Lot#BBC60830

Safety Data Sheet (MSDS): View Material Safety Data Sheet (MSDS)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

Additional Information

Bcl-2, Bcl-XL, and Bcl-w are frequently overexpressed in a wide variety of cancers, including those of the lymphatic system, breast, lung, prostate, and colon, and have been linked to tumor drug resistance.

References

1: Kaefer A, Yang J, Noertersheuser P, Mensing S, Humerickhouse R, Awni W, Xiong H. Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of navitoclax (ABT-263) induced thrombocytopenia. Cancer Chemother Pharmacol. 2014 Sep;74(3):593-602. doi: 10.1007/s00280-014-2530-9. Epub 2014 Jul 23. PubMed PMID: 25053389.

2: Yang J, Pradhan RS, Rosen LS, Graham AM, Holen KD, Xiong H. Effect of rifampin on the pharmacokinetics, safety and tolerability of navitoclax (ABT-263), a dual inhibitor of Bcl-2 and Bcl-X(L) , in patients with cancer. J Clin Pharm Ther. 2014 Jul 22. doi: 10.1111/jcpt.12193. [Epub ahead of print] PubMed PMID: 25047139.

3: Wei X, Zhou P, Lin X, Lin Y, Wu S, Diao P, Xie H, Xie K, Tang P. MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA. Tumour Biol. 2014 Jul 17. [Epub ahead of print] PubMed PMID: 25027405.

4: Suryani S, Carol H, Chonghaile TN, Frismantas V, Sarmah C, High L, Bornhauser B, Cowley MJ, Szymanska B, Evans K, Boehm I, Tonna E, Jones L, Manesh DM, Kurmasheva RT, Billups C, Kaplan W, Letai A, Bourquin JP, Houghton PJ, Smith MA, Lock RB. Cell and Molecular Determinants of In Vivo Efficacy of the BH3 Mimetic ABT-263 against Pediatric Acute Lymphoblastic Leukemia Xenografts. Clin Cancer Res. 2014 Sep 1;20(17):4520-31. doi: 10.1158/1078-0432.CCR-14-0259. Epub 2014 Jul 10. PubMed PMID: 25013123; PubMed Central PMCID: PMC4154988.

5: Polier G, Giaisi M, Köhler R, Müller WW, Lutz C, Buss EC, Krammer PH, Li-Weber M. Targeting CDK9 by wogonin and related natural flavones potentiates the anti-cancer efficacy of the Bcl-2 family inhibitor ABT-263. Int J Cancer. 2014 Jun 4. doi: 10.1002/ijc.29009. [Epub ahead of print] PubMed PMID: 24895203.

6: Vlahovic G, Karantza V, Wang D, Cosgrove D, Rudersdorf N, Yang J, Xiong H, Busman T, Mabry M. A phase I safety and pharmacokinetic study of ABT-263 in combination with carboplatin/paclitaxel in the treatment of patients with solid tumors. Invest New Drugs. 2014 Oct;32(5):976-84. doi: 10.1007/s10637-014-0116-3. Epub 2014 Jun 5. PubMed PMID: 24894650.

7: Wang X, Gu Z, Li G, Zhang S, Cao Z, Yang Z, Liu G. Norcantharidin enhances ABT-263-mediated anticancer activity in neuroblastoma cells by upregulation of Noxa. Oncol Rep. 2014 Aug;32(2):716-22. doi: 10.3892/or.2014.3228. Epub 2014 May 30. PubMed PMID: 24891300.

8: Wang B, Ni Z, Dai X, Qin L, Li X, Xu L, Lian J, He F. The Bcl-2/xL inhibitor ABT-263 increases the stability of Mcl-1 mRNA and protein in hepatocellular carcinoma cells. Mol Cancer. 2014 Apr 30;13:98. doi: 10.1186/1476-4598-13-98. PubMed PMID: 24779770; PubMed Central PMCID: PMC4021276.

9: Li J, Chen Y, Wan J, Liu X, Yu C, Li W. ABT-263 enhances sorafenib-induced apoptosis associated with Akt activity and the expression of Bax and p21((CIP1/WAF1)) in human cancer cells. Br J Pharmacol. 2014 Jul;171(13):3182-95. doi: 10.1111/bph.12659. PubMed PMID: 24571452; PubMed Central PMCID: PMC4080973.

10: Choo EF, Boggs J, Zhu C, Lubach JW, Catron ND, Jenkins G, Souers AJ, Voorman R. The role of lymphatic transport on the systemic bioavailability of the Bcl-2 protein family inhibitors navitoclax (ABT-263) and ABT-199. Drug Metab Dispos. 2014 Feb;42(2):207-12. doi: 10.1124/dmd.113.055053. Epub 2013 Nov 8. PubMed PMID: 24212376.