WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206541
CAS#: 1672665-49-4
Description: PT2385 is an orally active, small molecule inhibitor of hypoxia inducible factor (HIF)-2alpha, with potential antineoplastic activity. Upon oral administration, HIF-2alpha inhibitor PT2385 allosterically binds to HIF-2alpha, thereby preventing HIF-2alpha heterodimerization and its subsequent binding to DNA. This results in decreased transcription and expression of HIF-2alpha downstream target genes, many of which regulate tumor cell growth and survival.
MedKoo Cat#: 206541
Name: PT2385
CAS#: 1672665-49-4
Chemical Formula: C17H12F3NO4S
Exact Mass: 383.0439
Molecular Weight: 383.34
Elemental Analysis: C, 53.27; H, 3.16; F, 14.87; N, 3.65; O, 16.69; S, 8.36
Synonym: PT2385; PT-2385; PT 2385;
IUPAC/Chemical Name: (S)-3-((2,2-difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile
InChi Key: ONBSHRSJOPSEGS-INIZCTEOSA-N
InChi Code: InChI=1S/C17H12F3NO4S/c1-26(23,24)14-3-2-13(12-7-17(19,20)16(22)15(12)14)25-11-5-9(8-21)4-10(18)6-11/h2-6,16,22H,7H2,1H3/t16-/m0/s1
SMILES Code: CS(C(C=C1)=C2C(CC(F)(F)[C@H]2O)=C1OC3=CC(C#N)=CC(F)=C3)(=O)=O
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, 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).
HS Tariff Code: 2934.99.9001
| Biological target: | PT2385 is a selective HIF-2α antagonist with luciferase EC50 of 27 nM and no significant off-target activity. |
| In vitro activity: | This study investigated the benefits of using PT2385 to treat severe placental dysfunction. In vitro, RNA sequencing analysis and conventional techniques showed that PT2385 treated cytotrophoblast displayed an enhanced differentiation into syncytiotrophoblasts and normalized angiogenic factor secretion compared with vehicle-treated cells. Reference: Hypertension. 2023 May;80(5):1011-1023. https://pubmed.ncbi.nlm.nih.gov/36876500/ |
| In vivo activity: | PT2385 specifically targeted HIF2α, a key oncogenic driver in clear cell renal cell carcinoma, by blocking its dimerization with ARNT/HIF1β. This inhibition led to the suppression of HIF2α-dependent genes in tumor cells and resulted in dramatic tumor regressions when administered to tumor-bearing mice. PT2385 did not affect cardiovascular performance. Reference: Cancer Res. 2016 Sep 15;76(18):5491-500. https://pubmed.ncbi.nlm.nih.gov/27635045/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 50.0 | 130.43 |
The following data is based on the product molecular weight 383.34 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. Colson A, Depoix CL, Lambert I, Leducq C, Bedin M, De Beukelaer M, Gatto L, Loriot A, Peers de Nieuwburgh M, Bouhna K, Baldin P, Hubinont C, Sonveaux P, Debiève F. Specific HIF-2α (Hypoxia-Inducible Factor-2) Inhibitor PT2385 Mitigates Placental Dysfunction In Vitro and in a Rat Model of Preeclampsia (RUPP). Hypertension. 2023 May;80(5):1011-1023. doi: 10.1161/HYPERTENSIONAHA.122.20739. Epub 2023 Mar 6. PMID: 36876500. 2. Shen J, Xu L, Li Y, Dong W, Cai J, Liu Y, Zhao H, Xu T, Holtz EM, Chang Y, Qiao T, Li K. Protective Effects of Hif2 Inhibitor PT-2385 on a Neurological Disorder Induced by Deficiency of Irp2. Front Neurosci. 2021 Oct 5;15:715222. doi: 10.3389/fnins.2021.715222. PMID: 34675764; PMCID: PMC8525628. 3. Wallace EM, Rizzi JP, Han G, Wehn PM, Cao Z, Du X, Cheng T, Czerwinski RM, Dixon DD, Goggin BS, Grina JA, Halfmann MM, Maddie MA, Olive SR, Schlachter ST, Tan H, Wang B, Wang K, Xie S, Xu R, Yang H, Josey JA. A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma. Cancer Res. 2016 Sep 15;76(18):5491-500. doi: 10.1158/0008-5472.CAN-16-0473. Epub 2016 Sep 6. PMID: 27635045. |
| In vitro protocol: | 1. Colson A, Depoix CL, Lambert I, Leducq C, Bedin M, De Beukelaer M, Gatto L, Loriot A, Peers de Nieuwburgh M, Bouhna K, Baldin P, Hubinont C, Sonveaux P, Debiève F. Specific HIF-2α (Hypoxia-Inducible Factor-2) Inhibitor PT2385 Mitigates Placental Dysfunction In Vitro and in a Rat Model of Preeclampsia (RUPP). Hypertension. 2023 May;80(5):1011-1023. doi: 10.1161/HYPERTENSIONAHA.122.20739. Epub 2023 Mar 6. PMID: 36876500. |
| In vivo protocol: | 1. Shen J, Xu L, Li Y, Dong W, Cai J, Liu Y, Zhao H, Xu T, Holtz EM, Chang Y, Qiao T, Li K. Protective Effects of Hif2 Inhibitor PT-2385 on a Neurological Disorder Induced by Deficiency of Irp2. Front Neurosci. 2021 Oct 5;15:715222. doi: 10.3389/fnins.2021.715222. PMID: 34675764; PMCID: PMC8525628. 2. Wallace EM, Rizzi JP, Han G, Wehn PM, Cao Z, Du X, Cheng T, Czerwinski RM, Dixon DD, Goggin BS, Grina JA, Halfmann MM, Maddie MA, Olive SR, Schlachter ST, Tan H, Wang B, Wang K, Xie S, Xu R, Yang H, Josey JA. A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma. Cancer Res. 2016 Sep 15;76(18):5491-500. doi: 10.1158/0008-5472.CAN-16-0473. Epub 2016 Sep 6. PMID: 27635045. |
