WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 408068
CAS#: 2052128-15-9 (free base)
Description: H3B-5942 is a selective, irreversible and orally active estrogen receptor covalent antagonist. In vitro comparisons of H3B-5942 with standard-of-care (SoC) and experimental agents confirmed increased antagonist activity across a panel of ERαWT and ERαMUT cell lines. In vivo, H3B-5942 demonstrated significant single-agent antitumor activity in xenograft models representing ERαWT and ERαY537S breast cancer that was superior to fulvestrant.
MedKoo Cat#: 408068
Name: H3B-5942 free base
CAS#: 2052128-15-9 (free base)
Chemical Formula: C31H34N4O2
Exact Mass: 494.2682
Molecular Weight: 494.639
Elemental Analysis: C, 75.28; H, 6.93; N, 11.33; O, 6.47
Related CAS #: 2052132-46-2 (HCl) 2052128-15-9 (free base)
Synonym: H3B-5942; H3B 5942; H3B5942;
IUPAC/Chemical Name: (E)-4-((2-(4-((E)-1-(1H-indazol-5-yl)-2-phenylbut-1-en-1-yl)phenoxy)ethyl)amino)-N,N-dimethylbut-2-enamide
InChi Key: BYAUIDXIQATDBT-GIHLFXONSA-N
InChi Code: InChI=1S/C31H34N4O2/c1-4-28(23-9-6-5-7-10-23)31(25-14-17-29-26(21-25)22-33-34-29)24-12-15-27(16-13-24)37-20-19-32-18-8-11-30(36)35(2)3/h5-17,21-22,32H,4,18-20H2,1-3H3,(H,33,34)/b11-8+,31-28+
SMILES Code: CC/C(C1=CC=CC=C1)=C(C2=CC=C(OCCNC/C=C/C(N(C)C)=O)C=C2)\C3=CC(C=NN4)=C4C=C3
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: | H3B-5942 is a selective, irreversible and orally active estrogen receptor covalent antagonist, inactivates both wild-type and mutant ERα by targeting Cys530, with Kis of 1 nM and 0.41 nM, respectively. |
| In vitro activity: | In vitro comparisons of H3B-5942 with standard-of-care (SoC) and experimental agents confirmed increased antagonist activity across a panel of ERαWT and ERαMUT cell lines. Reference: Cancer Discov. 2018 Sep;8(9):1176-1193. https://pubmed.ncbi.nlm.nih.gov/29991605/ |
| In vivo activity: | In vivo, H3B-5942 demonstrated significant single-agent antitumor activity in xenograft models representing ERαWT and ERαY537S breast cancer that was superior to fulvestrant. Reference: Cancer Discov. 2018 Sep;8(9):1176-1193. https://pubmed.ncbi.nlm.nih.gov/29991605/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 60.65 | |
| DMF:PBS (pH 7.2) (1:3) | 0.25 | 0.51 | |
| DMSO | 61.11 | 123.54 | |
| Ethanol | 9.0 | 18.2 |
The following data is based on the product molecular weight 494.639 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.
| 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. Puyang X, Furman C, Zheng GZ, Wu ZJ, Banka D, Aithal K, Agoulnik S, Bolduc DM, Buonamici S, Caleb B, Das S, Eckley S, Fekkes P, Hao MH, Hart A, Houtman R, Irwin S, Joshi JJ, Karr C, Kim A, Kumar N, Kumar P, Kuznetsov G, Lai WG, Larsen N, Mackenzie C, Martin LA, Melchers D, Moriarty A, Nguyen TV, Norris J, O'Shea M, Pancholi S, Prajapati S, Rajagopalan S, Reynolds DJ, Rimkunas V, Rioux N, Ribas R, Siu A, Sivakumar S, Subramanian V, Thomas M, Vaillancourt FH, Wang J, Wardell S, Wick MJ, Yao S, Yu L, Warmuth M, Smith PG, Zhu P, Korpal M. Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer. Cancer Discov. 2018 Sep;8(9):1176-1193. doi: 10.1158/2159-8290.CD-17-1229. Epub 2018 Jul 10. PMID: 29991605. |
| In vitro protocol: | 1. Puyang X, Furman C, Zheng GZ, Wu ZJ, Banka D, Aithal K, Agoulnik S, Bolduc DM, Buonamici S, Caleb B, Das S, Eckley S, Fekkes P, Hao MH, Hart A, Houtman R, Irwin S, Joshi JJ, Karr C, Kim A, Kumar N, Kumar P, Kuznetsov G, Lai WG, Larsen N, Mackenzie C, Martin LA, Melchers D, Moriarty A, Nguyen TV, Norris J, O'Shea M, Pancholi S, Prajapati S, Rajagopalan S, Reynolds DJ, Rimkunas V, Rioux N, Ribas R, Siu A, Sivakumar S, Subramanian V, Thomas M, Vaillancourt FH, Wang J, Wardell S, Wick MJ, Yao S, Yu L, Warmuth M, Smith PG, Zhu P, Korpal M. Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer. Cancer Discov. 2018 Sep;8(9):1176-1193. doi: 10.1158/2159-8290.CD-17-1229. Epub 2018 Jul 10. PMID: 29991605. |
| In vivo protocol: | 1. Puyang X, Furman C, Zheng GZ, Wu ZJ, Banka D, Aithal K, Agoulnik S, Bolduc DM, Buonamici S, Caleb B, Das S, Eckley S, Fekkes P, Hao MH, Hart A, Houtman R, Irwin S, Joshi JJ, Karr C, Kim A, Kumar N, Kumar P, Kuznetsov G, Lai WG, Larsen N, Mackenzie C, Martin LA, Melchers D, Moriarty A, Nguyen TV, Norris J, O'Shea M, Pancholi S, Prajapati S, Rajagopalan S, Reynolds DJ, Rimkunas V, Rioux N, Ribas R, Siu A, Sivakumar S, Subramanian V, Thomas M, Vaillancourt FH, Wang J, Wardell S, Wick MJ, Yao S, Yu L, Warmuth M, Smith PG, Zhu P, Korpal M. Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer. Cancer Discov. 2018 Sep;8(9):1176-1193. doi: 10.1158/2159-8290.CD-17-1229. Epub 2018 Jul 10. PMID: 29991605. |
1. Puyang X, Furman C, Zheng GZ, et al. Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer. Cancer Discov. 2018;8(9):1176–1193. doi:10.1158/2159-8290.CD-17-1229
2. Furman C, Hao MH, Prajapati S, et al. Estrogen Receptor Covalent Antagonists: The Best Is Yet to Come. Cancer Res. 2019;79(8):1740–1745. doi:10.1158/0008-5472.CAN-18-3634
Mutations in estrogen receptor alpha (ERα) that confer resistance to existing classes of endocrine therapies are detected in up to 30% of patients who have relapsed during endocrine treatments. Because a significant proportion of therapy-resistant breast cancer metastases continue to be dependent on ERα signaling, there remains a critical need to develop the next generation of ERα antagonists that can overcome aberrant ERα activity.
