BMS-955176 free base
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MedKoo CAT#: 555297

CAS#: 1392312-45-6 (free base)

Description: GSK3532795, also known as BMS-955176, is a potent, orally active, second-generation HIV-1 maturation inhibitor (MI) that advanced through phase IIb clinical trials. GSK3532795 combines broad coverage of polymorphic viruses (EC50 <15 nM toward a panel of common polymorphisms representative of 96.5% HIV-1 subtype B virus) with a favorable pharmacokinetic profile in preclinical species.


Chemical Structure

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BMS-955176 free base
CAS# 1392312-45-6 (free base)

Theoretical Analysis

MedKoo Cat#: 555297
Name: BMS-955176 free base
CAS#: 1392312-45-6 (free base)
Chemical Formula: C42H62N2O4S
Exact Mass: 690.443
Molecular Weight: 691.028
Elemental Analysis: C, 73.00; H, 9.04; N, 4.05; O, 9.26; S, 4.64

Price and Availability

Size Price Availability Quantity
1.0mg USD 90.0 Ready to ship
5.0mg USD 350.0 Ready to ship
10.0mg USD 550.0 Ready to ship
25.0mg USD 1230.0 Ready to ship
50.0mg USD 2050.0 Ready to ship
100.0mg USD 3650.0 Ready to ship
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Related CAS #: 1392312-45-6 (free base)   2023808-13-9 (HCl)   2023798-97-0 (HCl hydrate)   2097784-79-5 (oxalate)   2097784-79-5 (TFA)    

Synonym: GSK3532795; GSK-3532795; GSK 3532795; BMS-955176; BMS 955176; BMS955176.

IUPAC/Chemical Name: 4‑((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)‑3a-((2-(1,1-Dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13boctadecahydro‑1H‑cyclopenta[a]chrysen-9-yl)benzoic Acid

InChi Key: XDMUFNNPLXHNKA-ZTESCHFWSA-N

InChi Code: InChI=1S/C42H62N2O4S/c1-28(2)31-14-19-42(43-22-23-44-24-26-49(47,48)27-25-44)21-20-40(6)33(36(31)42)12-13-35-39(5)17-15-32(29-8-10-30(11-9-29)37(45)46)38(3,4)34(39)16-18-41(35,40)7/h8-11,15,31,33-36,43H,1,12-14,16-27H2,2-7H3,(H,45,46)/t31-,33+,34-,35+,36+,39-,40+,41+,42-/m0/s1

SMILES Code: O=C(O)C1=CC=C(C2=CC[C@@]3(C)[C@@](C2(C)C)([H])CC[C@@]4(C)[C@]5(C)CC[C@](CC[C@H]6C(C)=C)(NCCN(CC7)CCS7(=O)=O)[C@@]6([H])[C@@]5([H])CC[C@]34[H])C=C1

Appearance: Solid powder

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

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

Shelf Life: >3 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).

HS Tariff Code: 2934.99.9001

Biological target: GSK3532795 (BMS-955176) is a potent, second-generation HIV-1 maturation inhibitor, with EC50s of 1.9, 10.2, 2.7 and 13 nM for HIV-1 WT, HIV-1 WT(human serum), HIV-1 V370A, and HIV-1 ΔV370, respectively.
In vitro activity: Longitudinal clinical isolates from 15 PI-treated patients and 7 highly PI-resistant (nonlongitudinal) viruses containing major and minor PI resistance-associated mutations were evaluated for GSK3532795 sensitivity. All nonlongitudinal viruses tested were sensitive to GSK3532795 (FC-IC50 range 0.16-0.68). Among longitudinal isolates, all post-PI treatment samples had major PI resistance-associated mutations in PR and 17/21 had PI resistance-associated changes in Gag. Nineteen of the 21 post-PI treatment samples had GSK3532795 CFB <3. Median (range) CFB was 0.83 (0.05-27.4) [Monogram (11 patients)] and 1.5 (1.0-2.2) [single-cycle (4 patients)]. The 2 post-PI treatment samples showing GSK3532795 CFB >3 (Monogram) were retested using single- and multiple-cycle assays. In conclusion, GSK3532795 maintained antiviral activity against PI-resistant isolates with emergent PR and/or Gag mutations. This finding supports continued development of GSK3532795 in treatment-experienced patients with or without previous PI therapy. Reference: J Acquir Immune Defic Syndr. 2017 May 1;75(1):52-60. https://pubmed.ncbi.nlm.nih.gov/28234686/
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 0.0 0.0

Preparing Stock Solutions

The following data is based on the product molecular weight 691.028 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Dicker I, Zhang S, Ray N, Beno BR, Regueiro-Ren A, Joshi S, Cockett M, Krystal M, Lataillade M. Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. PLoS One. 2019 Oct 17;14(10):e0224076. doi: 10.1371/journal.pone.0224076. Erratum in: PLoS One. 2019 Nov 5;14(11):e0224976. PMID: 31622432; PMCID: PMC6797179. 2. Ray N, Li T, Lin Z, Protack T, van Ham PM, Hwang C, Krystal M, Nijhuis M, Lataillade M, Dicker I. The Second-Generation Maturation Inhibitor GSK3532795 Maintains Potent Activity Toward HIV Protease Inhibitor-Resistant Clinical Isolates. J Acquir Immune Defic Syndr. 2017 May 1;75(1):52-60. doi: 10.1097/QAI.0000000000001304. PMID: 28234686; PMCID: PMC5389583.
In vitro protocol: 1. Dicker I, Zhang S, Ray N, Beno BR, Regueiro-Ren A, Joshi S, Cockett M, Krystal M, Lataillade M. Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. PLoS One. 2019 Oct 17;14(10):e0224076. doi: 10.1371/journal.pone.0224076. Erratum in: PLoS One. 2019 Nov 5;14(11):e0224976. PMID: 31622432; PMCID: PMC6797179. 2. Ray N, Li T, Lin Z, Protack T, van Ham PM, Hwang C, Krystal M, Nijhuis M, Lataillade M, Dicker I. The Second-Generation Maturation Inhibitor GSK3532795 Maintains Potent Activity Toward HIV Protease Inhibitor-Resistant Clinical Isolates. J Acquir Immune Defic Syndr. 2017 May 1;75(1):52-60. doi: 10.1097/QAI.0000000000001304. PMID: 28234686; PMCID: PMC5389583.
In vivo protocol: TBD

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1: Swidorski JJ, Jenkins S, Hanumegowda U, Parker DD, Beno BR, Protack T, Ng A, Gupta A, Shanmugam Y, Dicker IB, Krystal M, Meanwell NA, Regueiro-Ren A. Design and exploration of C-3 benzoic acid bioisosteres and alkyl replacements in the context of GSK3532795 (BMS-955176) that exhibit broad spectrum HIV-1 maturation inhibition. Bioorg Med Chem Lett. 2021 Mar 15;36:127823. doi: 10.1016/j.bmcl.2021.127823. Epub 2021 Jan 26. PMID: 33508465.

2: Regueiro-Ren A, Dicker IB, Hanumegowda U, Meanwell NA. Second Generation Inhibitors of HIV-1 Maturation. ACS Med Chem Lett. 2019 Feb 8;10(3):287-294. doi: 10.1021/acsmedchemlett.8b00656. PMID: 30891128; PMCID: PMC6421530.

3: Morales-Ramirez J, Bogner JR, Molina JM, Lombaard J, Dicker IB, Stock DA, DeGrosky M, Gartland M, Pene Dumitrescu T, Min S, Llamoso C, Joshi SR, Lataillade M. Safety, efficacy, and dose response of the maturation inhibitor GSK3532795 (formerly known as BMS-955176) plus tenofovir/emtricitabine once daily in treatment-naive HIV-1-infected adults: Week 24 primary analysis from a randomized Phase IIb trial. PLoS One. 2018 Oct 23;13(10):e0205368. doi: 10.1371/journal.pone.0205368. PMID: 30352054; PMCID: PMC6198970.

4: Regueiro-Ren A, Swidorski JJ, Liu Z, Chen Y, Sin N, Sit SY, Chen J, Venables BL, Zhu J, Nowicka-Sans B, Protack T, Lin Z, Terry B, Samanta H, Zhang S, Li Z, Easter J, Beno BR, Arora V, Huang XS, Rahematpura S, Parker DD, Haskell R, Santone KS, Cockett MI, Krystal M, Meanwell NA, Jenkins S, Hanumegowda U, Dicker IB. Design, Synthesis, and SAR of C-3 Benzoic Acid, C-17 Triterpenoid Derivatives. Identification of the HIV-1 Maturation Inhibitor 4-((1 R,3a S,5a R,5b R,7a R,11a S,11b R,13a R,13b R)-3a-((2-(1,1-Dioxidothiomorpholino)ethyl)ami no)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11 a,11b,12,13,13a,13b-octadecahydro-1 H-cyclopenta[ a]chrysen-9-yl)benzoic Acid (GSK3532795, BMS-955176). J Med Chem. 2018 Aug 23;61(16):7289-7313. doi: 10.1021/acs.jmedchem.8b00854. Epub 2018 Aug 1. PMID: 30067361.

5: Ortiz A, Soumeillant M, Savage SA, Strotman NA, Haley M, Benkovics T, Nye J, Xu Z, Tan Y, Ayers S, Gao Q, Kiau S. Synthesis of HIV-Maturation Inhibitor BMS-955176 from Betulin by an Enabling Oxidation Strategy. J Org Chem. 2017 May 5;82(9):4958-4963. doi: 10.1021/acs.joc.7b00438. Epub 2017 Apr 19. PMID: 28406018.

6: Strotman NA, Ortiz A, Savage SA, Wilbert CR, Ayers S, Kiau S. Revisiting a Classic Transformation: A Lossen Rearrangement Initiated by Nitriles and "Pseudo-Catalytic" in Isocyanate. J Org Chem. 2017 Apr 21;82(8):4044-4049. doi: 10.1021/acs.joc.7b00450. Epub 2017 Apr 12. PMID: 28394130.

7: Lin Z, Cantone J, Lu H, Nowicka-Sans B, Protack T, Yuan T, Yang H, Liu Z, Drexler D, Regueiro-Ren A, Meanwell NA, Cockett M, Krystal M, Lataillade M, Dicker IB. Mechanistic Studies and Modeling Reveal the Origin of Differential Inhibition of Gag Polymorphic Viruses by HIV-1 Maturation Inhibitors. PLoS Pathog. 2016 Nov 28;12(11):e1005990. doi: 10.1371/journal.ppat.1005990. PMID: 27893830; PMCID: PMC5125710.

8: Regueiro-Ren A, Liu Z, Chen Y, Sin N, Sit SY, Swidorski JJ, Chen J, Venables BL, Zhu J, Nowicka-Sans B, Protack T, Lin Z, Terry B, Samanta H, Zhang S, Li Z, Beno BR, Huang XS, Rahematpura S, Parker DD, Haskell R, Jenkins S, Santone KS, Cockett MI, Krystal M, Meanwell NA, Hanumegowda U, Dicker IB. Discovery of BMS-955176, a Second Generation HIV-1 Maturation Inhibitor with Broad Spectrum Antiviral Activity. ACS Med Chem Lett. 2016 Apr 22;7(6):568-72. doi: 10.1021/acsmedchemlett.6b00010. PMID: 27326328; PMCID: PMC4904268.

9: Nowicka-Sans B, Protack T, Lin Z, Li Z, Zhang S, Sun Y, Samanta H, Terry B, Liu Z, Chen Y, Sin N, Sit SY, Swidorski JJ, Chen J, Venables BL, Healy M, Meanwell NA, Cockett M, Hanumegowda U, Regueiro-Ren A, Krystal M, Dicker IB. Identification and Characterization of BMS-955176, a Second-Generation HIV-1 Maturation Inhibitor with Improved Potency, Antiviral Spectrum, and Gag Polymorphic Coverage. Antimicrob Agents Chemother. 2016 Jun 20;60(7):3956-69. doi: 10.1128/AAC.02560-15. PMID: 27090171; PMCID: PMC4914680.

10: Gulick RM. Choosing Initial Antiretroviral Therapy: Current Recommendations for Initial Therapy and Newer or Investigational Agents. Top Antivir Med. 2015 Oct-Nov;23(4):128-31. PMID: 26713502; PMCID: PMC6148919.

11: Olender SA, Taylor BS, Wong M, Wilkin TJ. CROI 2015: Advances in Antiretroviral Therapy. Top Antivir Med. 2015 Mar-Apr;23(1):28-45. PMID: 25965310; PMCID: PMC6148902.