PT2385 | CAS#1672665-49-4 | a potent HIF-2α inhibitor

MedKoo Cat#: 206541 | Name: PT2385

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

PT2385

CAS#1672665-49-4

Theoretical Analysis

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

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to Ship
500mg	USD 2,650.00	Ready to Ship
1g	USD 3,950.00	Ready to Ship

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Related CAS #

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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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C21R06B07

QC Data

View QC data: current batch, Lot#C21R06B07

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	50.0	130.43

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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:

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.

1: Sun X, Sun BL, Sammani S, Dudek SM, Belvitch P, Camp SM, Zhang DD, Bime C, Garcia JGN. Genetic and Epigenetic Regulation of Cortactin (CTTN) by Inflammatory Factors and Mechanical Stress in Human Lung Endothelial Cells. Biosci Rep. 2024 Aug 20:BSR20231934. doi: 10.1042/BSR20231934. Epub ahead of print. PMID: 39162263. 2: Janssens LK, Stove CP. The 'ABC' of split-nanoluciferase HIF heterodimerization bioassays: Applications, Benefits & Considerations. Biochem Pharmacol. 2024 Aug 10;229:116478. doi: 10.1016/j.bcp.2024.116478. Epub ahead of print. PMID: 39128589. 3: Cheng C, Xing Z, Zhang W, Zheng L, Zhao H, Zhang X, Ding Y, Qiao T, Li Y, Meyron-Holtz EG, Missirlis F, Fan Z, Li K. Iron regulatory protein 2 contributes to antimicrobial immunity by preserving lysosomal function in macrophages. Proc Natl Acad Sci U S A. 2024 Jul 30;121(31):e2321929121. doi: 10.1073/pnas.2321929121. Epub 2024 Jul 24. PMID: 39047035; PMCID: PMC11295080. 4: Li K, Luobu G, Wu P, Ciren D, Xiao X, Li K, Li Q. Ameliorating effects of the HIF-2α inhibitor PT2385 on high-altitude polycythemia. Eur J Pharm Sci. 2024 Jul 18;201:106857. doi: 10.1016/j.ejps.2024.106857. Epub ahead of print. PMID: 39032535. 5: Wang X, Zhou S, Hu X, Ye C, Nie Q, Wang K, Yan S, Lin J, Xu F, Li M, Wu Q, Sun L, Liu B, Zhang Y, Yun C, Wang X, Liu H, Yin WB, Zhao D, Hang J, Zhang S, Jiang C, Pang Y. Candida albicans accelerates atherosclerosis by activating intestinal hypoxia-inducible factor2α signaling. Cell Host Microbe. 2024 Jun 12;32(6):964-979.e7. doi: 10.1016/j.chom.2024.04.017. Epub 2024 May 15. PMID: 38754418. 6: Yin A, Fu W, Elengickal A, Kim J, Liu Y, Bigot A, Mamchaoui K, Call JA, Yin H. Chronic hypoxia impairs skeletal muscle repair via HIF-2α stabilization. J Cachexia Sarcopenia Muscle. 2024 Apr;15(2):631-645. doi: 10.1002/jcsm.13436. Epub 2024 Feb 9. PMID: 38333911; PMCID: PMC10995261. 7: Liu R, Zou Z, Chen L, Feng Y, Ye J, Deng Y, Zhu X, Zhang Y, Lin J, Cai S, Tang Z, Liang Y, Lu J, Zhuo Y, Han Z, Ling X, Liang Y, Wang Z, Zhong W. FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to the HIF2α blockade by facilitating LDHA phosphorylation. Cell Death Dis. 2024 Jan 17;15(1):64. doi: 10.1038/s41419-024-06450-x. PMID: 38233415; PMCID: PMC10794466. 8: Zhou S, Yan J, Song K, Ge RL. High-Altitude Hypoxia Induces Excessive Erythrocytosis in Mice via Upregulation of the Intestinal HIF2a/Iron- Metabolism Pathway. Biomedicines. 2023 Nov 7;11(11):2992. doi: 10.3390/biomedicines11112992. PMID: 38001992; PMCID: PMC10669251. 9: Strowd R, Ellingson B, Raymond C, Yao J, Wen PY, Ahluwalia M, Piotrowski A, Desai A, Clarke JL, Lieberman FS, Desideri S, Nabors LB, Ye X, Grossman S. Activity of a first-in-class oral HIF2-alpha inhibitor, PT2385, in patients with first recurrence of glioblastoma. J Neurooncol. 2023 Oct;165(1):101-112. doi: 10.1007/s11060-023-04456-7. Epub 2023 Oct 21. PMID: 37864646; PMCID: PMC10863646. 10: Morris DR, Qu Y, Jones-Hall YL, Liu T, Ivanciuc T, Garofalo RP, Casola A. Hypoxia-inducible-factors differentially contribute to clinical disease and the control of viral replication during RSV infection. bioRxiv [Preprint]. 2023 Dec 13:2023.08.15.553422. doi: 10.1101/2023.08.15.553422. PMID: 37645750; PMCID: PMC10461990. 11: 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. 12: Yang Y, Chen W, Mai W, Gao Y. HIF-2α regulates proliferation, invasion, and metastasis of hepatocellular carcinoma cells via VEGF/Notch1 signaling axis after insufficient radiofrequency ablation. Front Oncol. 2022 Sep 23;12:998295. doi: 10.3389/fonc.2022.998295. PMID: 36212390; PMCID: PMC9539942. 13: Philip M, Karakka Kal AK, Mathew B, Subhahar MB, Karatt TK, Perwad Z. Metabolic study of hypoxia-inducible factor stabilizers BAY 87-2243, MK-8617, and PT-2385 in equine liver microsomes for doping control. Drug Test Anal. 2022 Oct;14(10):1703-1723. doi: 10.1002/dta.3348. Epub 2022 Jul 26. PMID: 35853151. 14: Chen M, Shu G, Lv X, Xu X, Lu C, Qiao E, Fang S, Shen L, Zhang N, Wang J, Chen C, Song J, Liu Z, Du Y, Ji J. HIF-2α-targeted interventional chemoembolization multifunctional microspheres for effective elimination of hepatocellular carcinoma. Biomaterials. 2022 May;284:121512. doi: 10.1016/j.biomaterials.2022.121512. Epub 2022 Apr 5. Erratum in: Biomaterials. 2024 Dec;311:122676. doi: 10.1016/j.biomaterials.2024.122676. PMID: 35405577. 15: Moog S, Salgues B, Braik-Djellas Y, Viel T, Balvay D, Autret G, Robidel E, Gimenez-Roqueplo AP, Tavitian B, Lussey-Lepoutre C, Favier J. Preclinical evaluation of targeted therapies in Sdhb-mutated tumors. Endocr Relat Cancer. 2022 May 11;29(6):375-388. doi: 10.1530/ERC-22-0030. PMID: 35348472. 16: Qin Y, Zhang J, Babapoor-Farrokhran S, Applewhite B, Deshpande M, Megarity H, Flores-Bellver M, Aparicio-Domingo S, Ma T, Rui Y, Tzeng SY, Green JJ, Canto- Soler MV, Montaner S, Sodhi A. PAI-1 is a vascular cell-specific HIF-2-dependent angiogenic factor that promotes retinal neovascularization in diabetic patients. Sci Adv. 2022 Mar 4;8(9):eabm1896. doi: 10.1126/sciadv.abm1896. Epub 2022 Mar 2. PMID: 35235351; PMCID: PMC8890718. 17: Yoo SJ, Lee HR, Kim J, Yoo IS, Park CK, Kang SW. Hypoxia-Inducible Factor-2 Alpha Regulates the Migration of Fibroblast-like Synoviocytes via Oxidative Stress-Induced CD70 Expression in Patients with Rheumatoid Arthritis. Int J Mol Sci. 2022 Feb 20;23(4):2342. doi: 10.3390/ijms23042342. PMID: 35216458; PMCID: PMC8877612. 18: Elias R, Tcheuyap VT, Kaushik AK, Singla N, Gao M, Reig Torras O, Christie A, Mulgaonkar A, Woolford L, Stevens C, Kettimuthu KP, Pavia-Jimenez A, Boroughs LK, Joyce A, Dakanali M, Notgrass H, Margulis V, Cadeddu JA, Pedrosa I, Williams NS, Sun X, DeBerardinis RJ, Öz OK, Zhong H, Seshagiri S, Modrusan Z, Cantarel BL, Kapur P, Brugarolas J. A renal cell carcinoma tumorgraft platform to advance precision medicine. Cell Rep. 2021 Nov 23;37(8):110055. doi: 10.1016/j.celrep.2021.110055. PMID: 34818533; PMCID: PMC8762721. 19: 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. 20: Zheng Q, Lu W, Yan H, Duan X, Chen Y, Zhang C, Luo X, Chen J, Wang C, Liu S, Li Y, Tang H, Rahimi S, Rahimi S, Yuan JX, Zhong N, Yang K, Wang J. Established pulmonary hypertension in rats was reversed by a combination of a HIF-2α antagonist and a p53 agonist. Br J Pharmacol. 2022 Mar;179(5):1065-1081. doi: 10.1111/bph.15696. Epub 2021 Nov 16. PMID: 34599843.