PT-2385

• CAT Number: I002185
• CAS Number: 1672665-49-4
• Molecular Formula: C₁₇H₁₂F₃NO₄S
• Molecular Weight: 383.34
• Purity: ≥95%
• Synonyms: PT-2385; PT 2385;PT2385
• Target: HIF/HIF Prolyl-Hydroxylase
• Solubility: 10 mM in DMSO
• Storage: 3 years -20℃ powder
• IUPAC Name: 3-[[(1S)-2,2-difluoro-1-hydroxy-7-methylsulfonyl-1,3-dihydroinden-4-yl]oxy]-5-fluorobenzonitrile
• InChI: 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
• InChIKey: ONBSHRSJOPSEGS-INIZCTEOSA-N
• SMILES: CS(=O)(=O)C1=C2C(C(CC2=C(C=C1)OC3=CC(=CC(=C3)C#N)F)(F)F)O

PT-2385 (Cat.No:I002185) is an investigational drug targeting hypoxia-inducible factor 2-alpha (HIF-2α), a protein involved in tumor growth and progression. As a HIF-2α inhibitor, PT-2385 has shown promise in preclinical studies for the treatment of clear cell renal cell carcinoma (ccRCC) and other HIF-2α-driven cancers. Clinical trials are ongoing to assess its efficacy and safety in cancer therapy.

Reference

1. Cell Death Dis. 2017 Oct 12;8(10):e3095. doi: 10.1038/cddis.2017.411.

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of
sorafenib by suppressing hepatocellular carcinoma invasion via alteration of
pSTAT3, pAKT and pERK signals.

Xu J(1), Zheng L(1), Chen J(1), Sun Y(2), Lin H(1), Jin RA(1), Tang M(3), Liang
X(1), Cai X(1).
Author information:
(1)Key Laboratory of Endoscopic Technique Research of Zhejiang Province,
Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University,
Hangzhou 310016, China.
(2)Department of Radiation Oncology, University of Rochester Medical Center,
Rochester, NY 14642, USA.
(3)Department of Reproductive Endocrinology, Women/’s Hospital, School of
Medicine, Zhejiang University, Hangzhou 310006, China.

Although sorafenib is currently used as a standard treatment for advanced
hepatocellular carcinoma, low response rate, transient and limited efficacy,
primary and acquired resistance and negative side-effects gain increasing
attentions, suggesting the need for better efficacious combination therapy. Here,
we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible
factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region
of androgen receptor (AR) promoter and thus transcriptionally suppress AR.
Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α
inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing
HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways.
Clinical samples further confirmed the role of HIF-2α and AR. It is promising
that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment
by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC
patients.