ABT-263

• CAT Number: I005495
• CAS Number: 923564-51-6
• Molecular Formula: C₄₅H₅₅ClF₃N₅O₆S₃
• Molecular Weight: 974.61
• Purity: ≥95%
• Synonyms: ABT-263;ABT263
• Target: Bcl-2 Family
• Solubility: DMSO ≥190mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL
• Storage: 3 years -20C powder
• IC50: ≤ 0.5 nM(Ki for Bcl-xL); ≤1 nM(Ki for Bcl-2); ≤1 nM(Ki for Bcl-w)
• InChI: 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
• InChIKey: JLYAXFNOILIKPP-KXQOOQHDSA-N
• 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

ABT-263 (Navitoclax) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤1 nM. 


in vitro: ABT-263 displays the protection afforded by overexpression of Bcl-2 or Bcl-xL with EC50 values of 60 nM and 20 nM, respectively. A wide range of cellular activity is observed with 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 μM. All four cell lines with EC50 values of <400 nM (H146, H889, H1963, and H1417) are also highly sensitive to ABT-737, and the two most resistant lines (H1048 and H82) are similarly resistant to ABT-263. 


in vivo: ABT-263 is administered at 100 mg/kg/day in the H345 xenograft model, significant antitumor efficacy is observed with 80% TGI and 20% of treated tumors indicating at least a 50% reduction in tumor volume. Oral administration of ABT-263 alone causes complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 displays modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens.

Reference

1:Data on the DNA damaging and mutagenic potential of the BH3-mimetics ABT-263/Navitoclax and TW-37. Green MM, Shekhar TM, Hawkins CJ.Data Brief. 2016 Jan 16;6:710-4. doi: 10.1016/j.dib.2016.01.013. eCollection 2016 Mar. PMID: 26958630 Free PMC Article2:Augmented efficacy of brentuximab vedotin combined with ruxolitinib and/or Navitoclax in a murine model of human Hodgkin/’s lymphoma. Ju W, Zhang M, Wilson KM, Petrus MN, Bamford RN, Zhang X, Guha R, Ferrer M, Thomas CJ, Waldmann TA.Proc Natl Acad Sci U S A. 2016 Feb 9;113(6):1624-9. doi: 10.1073/pnas.1524668113. Epub 2016 Jan 25. PMID: 26811457 Free PMC Article3:Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, Dai HM, Ling YY, Stout MB, Pirtskhalava T, Giorgadze N, Johnson KO, Giles CB, Wren JD, Niedernhofer LJ, Robbins PD, Kirkland JL.Aging Cell. 2016 Jun;15(3):428-35. doi: 10.1111/acel.12445. Epub 2016 Mar 18. PMID: 26711051 Free PMC Article4:Combination with vorinostat overcomes ABT-263 (navitoclax) resistance of small cell lung cancer. Nakajima W, Sharma K, Hicks MA, Le N, Brown R, Krystal GW, Harada H.Cancer Biol Ther. 2016;17(1):27-35. doi: 10.1080/15384047.2015.1108485. PMID: 26575826 Free PMC Article5:A tenascin C targeted nanoliposome with navitoclax for specifically eradicating of cancer-associated fibroblasts. Chen B, Wang Z, Sun J, Song Q, He B, Zhang H, Wang X, Dai W, Zhang Q.Nanomedicine. 2016 Jan;12(1):131-41. doi: 10.1016/j.nano.2015.10.001. Epub 2015 Oct 27. PMID: 26518604 6:Clearance of systemic hematologic tumors by venetoclax (Abt-199) and navitoclax. Ackler S, Oleksijew A, Chen J, Chyla BJ, Clarin J, Foster K, McGonigal T, Mishra S, Schlessinger S, Smith ML, Tahir SK, Leverson JD, Souers AJ, Boghaert ER, Hickson J.Pharmacol Res Perspect. 2015 Oct;3(5):e00178. doi: 10.1002/prp2.178. Epub 2015 Sep 1. PMID: 26516589 Free PMC Article7:Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with irinotecan: results of an open-label, phase 1 study. Tolcher AW, LoRusso P, Arzt J, Busman TA, Lian G, Rudersdorf NS, Vanderwal CA, Waring JF, Yang J, Holen KD, Rosen LS.Cancer Chemother Pharmacol. 2015 Nov;76(5):1041-9. doi: 10.1007/s00280-015-2882-9. Epub 2015 Oct 1. PMID: 26429709 8:Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with erlotinib in patients with advanced solid tumors. Tolcher AW, LoRusso P, Arzt J, Busman TA, Lian G, Rudersdorf NS, Vanderwal CA, Kirschbrown W, Holen KD, Rosen LS.Cancer Chemother Pharmacol. 2015 Nov;76(5):1025-32. doi: 10.1007/s00280-015-2883-8. Epub 2015 Sep 29. PMID: 26420235 9:HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expression. Witzens-Harig M, Giaisi M, Köhler R, Krammer PH, Li-Weber M.Int J Cancer. 2016 Jan 15;138(2):507-14. doi: 10.1002/ijc.29726. Epub 2015 Aug 27. PMID: 26260669 Free Article10:Phase 1 study of the safety, pharmacokinetics, and antitumour activity of the BCL2 inhibitor navitoclax in combination with rituximab in patients with relapsed or refractory CD20+ lymphoid malignancies. Roberts AW, Advani RH, Kahl BS, Persky D, Sweetenham JW, Carney DA, Yang J, Busman TB, Enschede SH, Humerickhouse RA, Seymour JF.Br J Haematol. 2015 Sep;170(5):669-78. doi: 10.1111/bjh.13487. Epub 2015 May 5. PMID: 25942994 Free PMC Article