Delving into the Latest Updates on CYH33 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Risovalisib

+ [2]

Target

PI3Kα

Action

inhibitors

Mechanism

PI3Kα inhibitors(Phosphatidylinositol 3 kinase alpha inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [4]

Active Indication

Fallopian Tube Clear Cell AdenocarcinomaOvarian clear cell carcinomaPrimary clear cell peritoneal carcinoma+ [4]

Inactive Indication

Advanced breast cancerEndometrial CarcinomaEsophageal Carcinoma+ [8]

Originator Organization

Haihe Biopharma Co., Ltd.

Active Organization

Haihe Biopharma Co., Ltd.

Shanghai Institute of Materia Medica Chinese Academy of Sci

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationSpecial Review Project (China)

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Structure/Sequence

Molecular FormulaC25H33F3N8O8S2

InChIKeyCYWUJTNXNJVGLY-UHFFFAOYSA-N

CAS Registry1494684-33-1

View All Structures (2)

主要目的： - 采用盲态独立评审委员会（BIRC）评估的客观缓解率（ORR）来确定CYH33单药治疗在具有PIK3CA热点突变的复发性或持续性卵巢、输卵管或原发性腹膜透明细胞癌患者中的有效性。将采用顺序检验依次评估主要目的，首先在具有PIK3CA外显子9突变的患者中进行评估，然后在所有PIK3CA热点突变的患者中进行评估。次要目的： - 评价CYH33经BIRC评估的无进展生存期（PFS）、6个月PFS率、缓解持续时间（DoR）、至缓解的时间（TTR）和疾病控制率（DCR）方面的有效性。 - 评价CYH33经研究者评估的ORR、PFS、6个月PFS率、DoR、TTR和DCR方面的有效性。 - 评价总体生存期（OS）获益。

[Translation]

Primary Objectives: - To determine the efficacy of CYH33 monotherapy in patients with recurrent or persistent ovarian, fallopian tube, or primary peritoneal clear cell carcinoma with PIK3CA hotspot mutations using blinded independent review committee (BIRC)-assessed objective response rate (ORR). The primary objectives will be assessed sequentially, first in patients with PIK3CA exon 9 mutations and then in patients with all PIK3CA hotspot mutations, using sequential testing. Secondary Objectives: - To evaluate the efficacy of CYH33 in terms of BIRC-assessed progression-free survival (PFS), 6-month PFS rate, duration of response (DoR), time to response (TTR), and disease control rate (DCR). - To evaluate the efficacy of CYH33 in terms of investigator-assessed ORR, PFS, 6-month PFS rate, DoR, TTR, and DCR. - To evaluate the overall survival (OS) benefit.

Start Date12 Jul 2022

Sponsor / Collaborator

Haihe Biopharma Co., Ltd.

[+1]

CTR20211864

/ CompletedPhase 1

一项在中国健康成人中评价食物对CYH33单次给药后的药代动力学特征和安全性影响的临床研究

[Translation] A clinical study to evaluate the effect of food on the pharmacokinetic characteristics and safety of CYH33 after a single dose in healthy Chinese adults

主要目的：评价食物对中国健康成人受试者单次口服CYH33药代动力学特征的影响。次要目的：评价食物对中国健康成人受试者单次口服CYH33安全性的影响。评价CYH33药效动力学生物标志物的变化。

[Translation]

Primary objective: To evaluate the effect of food on the pharmacokinetic characteristics of CYH33 after a single oral dose in healthy Chinese adult subjects. Secondary objective: To evaluate the effect of food on the safety of a single oral dose of CYH33 in healthy Chinese adult subjects. To evaluate the changes in CYH33 pharmacodynamic biomarkers.

Start Date10 Jun 2022

Sponsor / Collaborator

Haihe Biopharma Co., Ltd.

[+1]

100 Clinical Results associated with CYH33

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100 Translational Medicine associated with CYH33

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100 Patents (Medical) associated with CYH33

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15

Literatures (Medical) associated with CYH33

01 Nov 2024·Biochemical and Biophysical Research Communications

Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling

Article

Author: Obata, Yoshinari ; Kawada, Keitaro ; Fukuda, Shiro ; Nishizawa, Hitoshi ; Kimura, Tadashi ; Okita, Tomonori ; Matsumoto, Hisatake ; Fukuoka, Keita ; Nakagawa, Satoshi ; Shimomura, Iichiro ; Nagao, Hirofumi ; Fujishima, Yuya ; Iioka, Masahito ; Kita, Shunbun ; Kondo, Yuta ; Sakaue, Taka-Aki ; Ebihara, Takeshi

AIM AND OBJECTIVEOur recent report showed that soluble T-cadherin promotes pancreatic beta-cell proliferation. However, how and where the secretion of soluble T-cadherin is regulated remain unclear.METHODS AND RESULTSSoluble T-cadherin levels significantly increased in leptin receptor-deficient db/db mice with hypoinsulinaemia or in wild-type mice treated with insulin receptor blockade by S961. Similar results were observed in human subjects; Diabetic ketoacidosis patients at the time of hospitalization had increased plasma soluble T-cadherin levels, which decreased after insulin infusion therapy. Patients with recurrent ovarian cancer who were administered a phosphatidylinositol-3 kinase (PI3K)-alpha inhibitor (a new anticancer drug) had increased plasma soluble T-cadherin and plasma C-peptide levels. Endothelial cell-specific T-cadherin knockout mice, but not skeletal muscle- or cardiac muscle-specific T-cadherin knockout mice, showed a 26 % reduction in plasma soluble T-cadherin levels and a significant increase in blood glucose levels in streptozocin-induced diabetes. The secretion of soluble T-cadherin from human endothelial cells was approximately 20 % decreased by insulin and this decrease was canceled by blockade of insulin receptor/Akt signalling, not Erk signalling.CONCLUSIONWe conclude that insulin regulates soluble T-cadherin levels and soluble T-cadherin secretion from endothelial cells is positively regulated by insulin/insulin receptor/Akt signalling.

01 Nov 2024·Molecular Oncology

Cell‐free DNA from ascites identifies clinically relevant variants and tumour evolution in patients with advanced ovarian cancer

Article

Author: Arora, Vivek ; Powell, Elyse ; Athavale, Ramanand ; Lee, Yeh Chen ; Ford, Caroline E. ; Cortesi, Marilisa ; Warton, Kristina ; Werner, Bonnita ; Dean, Michael ; Duggan, Jennifer

The emergence of targeted therapies has transformed ovarian cancer treatment. However, biomarker profiling for precision medicine is limited by access to quality, tumour‐enriched tissue samples. The use of cell‐free DNA (cfDNA) in ascites presents a potential solution to this challenge. In this study, next‐generation sequencing was performed on ascites‐derived cfDNA samples (26 samples from 15 human participants with ovarian cancer), with matched DNA from ascites‐derived tumour cells (n = 5) and archived formalin‐fixed paraffin‐embedded (FFPE) tissue (n = 5). Similar tumour purity and variant detection were achieved with cfDNA compared to FFPE and ascites cell DNA. Analysis of large‐scale genomic alterations, loss of heterozygosity and tumour mutation burden identified six cases of high genomic instability (including four with pathogenic BRCA1 and BRCA2 mutations). Copy number profiles and subclone prevalence changed between sequential ascites samples, particularly in a case where deletions and chromothripsis in Chr17p13.1 and Chr8q resulted in changes in clinically relevant TP53 and MYC variants over time. Ascites cfDNA identified clinically actionable information, concordant to tissue biopsies, enabling opportunistic molecular profiling. This advocates for analysis of ascites cfDNA in lieu of accessing tumour tissue via biopsy.

01 May 2023·Acta Pharmacologica Sinica

Targeting PI3Kα overcomes resistance to KRasG12C inhibitors mediated by activation of EGFR and/or IGF1R

Article

Author: Qi, Wei-Liang ; Zhang, Xi ; Meng, Ling-Hua ; Li, Hui-Yu ; Deng, Jie-Ting ; Wang, Yi ; Wang, Yu-Xiang ; Xu, Lan

Although several KRas^G12C inhibitors have displayed promising efficacy in clinical settings, acquired resistance developed rapidly and circumvented the activity of KRas^G12C inhibitors. To explore the mechanism rendering acquired resistance to KRas^G12C inhibitors, we established a series of KRAS^G12C-mutant cells with acquired resistance to AMG510. We found that differential activation of receptor tyrosine kinases (RTKs) especially EGFR or IGF1R rendered resistance to AMG510 in different cellular contexts by maintaining the activation of MAPK and PI3K signaling. Simultaneous inhibition of EGFR and IGF1R restored sensitivity to AMG510 in resistant cells. PI3K integrates signals from multiple RTKs and the level of phosphorylated AKT was revealed to negatively correlate with the anti-proliferative activity of AMG510 in KRAS^G12C-mutant cells. Concurrently treatment of a novel PI3Kα inhibitor CYH33 with AMG510 exhibited a synergistic effect against parental and resistant KRAS^G12C-mutant cells in vitro and in vivo, which was accompanied with concomitant inhibition of AKT and MAPK signaling. Taken together, these findings revealed the potential mechanism rendering acquired resistance to KRas^G12C inhibitors and provided a mechanistic rationale to combine PI3Kα inhibitors with KRas^G12C inhibitors for therapy of KRAS^G12C-mutant cancers in future clinical trials.

100 Deals associated with CYH33

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
PIK3CA-related overgrowth syndrome	Phase 2	China	Haihe Biopharma Co., Ltd.	10 Aug 2023
PIK3CA-related vascular malformations	Phase 2	China	Haihe Biopharma Co., Ltd.	10 Aug 2023
Fallopian Tube Clear Cell Adenocarcinoma	Phase 2	China	Shanghai Institute of Materia Medica Chinese Academy of Sci	12 Jul 2022
Fallopian Tube Clear Cell Adenocarcinoma	Phase 2	China	Haihe Biopharma Co., Ltd.	12 Jul 2022
Ovarian clear cell carcinoma	Phase 2	Japan	Haihe Biopharma Co., Ltd.	13 Aug 2021
Ovarian clear cell carcinoma	Phase 2	China	Haihe Biopharma Co., Ltd.	13 Aug 2021
Primary clear cell peritoneal carcinoma	Phase 2	China	Haihe Biopharma Co., Ltd.	13 Aug 2021
Primary clear cell peritoneal carcinoma	Phase 2	Japan	Haihe Biopharma Co., Ltd.	13 Aug 2021
Advanced Malignant Solid Neoplasm	Phase 1	China	Haihe Biopharma Co., Ltd.	17 May 2018
Esophageal Carcinoma	Discovery	China	Haihe Biopharma Co., Ltd.	10 May 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04856371 (ASCO2024) Manual	Phase 1	PIK3CA mutation/HR-positive/HER2-negative Breast Cancer \| \|	52	CYH33 + Fulvestrant	(mgoyxzffxq) = CYH33 30mg QD + Fulvestrant 500mg gicxiwvkub (wrhrqdkmpc ) View more	Positive	24 May 2024
				CYH33 + Fulvestrant (PIK3CA-mutations without prior fulvestrant treatment)
NCT03544905 (Pubmed) Manual	Phase 1	PIK3CA H1047R mutant Solid Tumors PIK3CA Mutation	51	CYH33 (overall)	(leaywoyuzm) = nziqkrqoxk bljelknytv (ckttiacukm ) View more	Positive	16 Nov 2022
				CYH33 (patients with PIK3CA mutations)	(fuisgpytfd) = yjlyfakymd impltqiefc (mpojyrkhqy )