Delving into the Latest Updates on AST-001 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

17β-HSD5

Mechanism

17β-HSD5 stimulants(Aldo-keto-reductase family 1 member C3 stimulants)

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [4]

Active Indication

NeoplasmsAdvanced Malignant Solid NeoplasmBreast Cancer+ [11]

Inactive Indication-

Originator Organization

Ascentawits Pharmaceuticals Ltd.Startup

Active Organization

Ascentawits Pharmaceuticals Ltd.Startup

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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主要目的： - 评估实体瘤受试者接受AST-001静脉输注给药的安全性和耐受性 - 评估实体瘤受试者中AST-001及其主要代谢产物AST 2660的药代动力学特征 - 确定实体瘤受试者接受AST-001单药治疗的最大耐受剂量（MTD），并确定II期临床推荐剂量（RP2D）次要目的： - 根据受试者的客观缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DOR）和无进展生存期（PFS）初步评估AST-001单药治疗恶性肿瘤的疗效 - 探索肿瘤组织经免疫组织化学（IHC）确定的AKR1C3表达与疗效之间的关系 - 评估AST-001在人体内的代谢产物谱探索性目的: - 探索DNA损伤修复相关基因的突变情况

[Translation]

Primary objectives: - To evaluate the safety and tolerability of AST-001 intravenous infusion in subjects with solid tumors - To evaluate the pharmacokinetic characteristics of AST-001 and its main metabolite AST 2660 in subjects with solid tumors - To determine the maximum tolerated dose (MTD) of AST-001 monotherapy in subjects with solid tumors and determine the recommended dose (RP2D) for Phase II clinical trials Secondary objectives: - To preliminarily evaluate the efficacy of AST-001 monotherapy in the treatment of malignant tumors based on the objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS) of the subjects - To explore the relationship between AKR1C3 expression determined by immunohistochemistry (IHC) in tumor tissues and efficacy - To evaluate the metabolite spectrum of AST-001 in humans Exploratory objectives: - To explore the mutation status of genes related to DNA damage repair

Start Date01 Jul 2022

Sponsor / Collaborator

Ascentawits Pharmaceuticals Ltd.Startup

KCT0005915 / CompletedPhase 1

A randomized, open-label, single and multiple ascending dose phase 1 clinical trial to investigate the pharmacokinetic and tolerability of AST-001 administration in healthy subjects

Start Date02 Jul 2020

Sponsor / Collaborator

Astrogen Co., Ltd.Startup

100 Clinical Results associated with AST-001

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100 Translational Medicine associated with AST-001

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100 Patents (Medical) associated with AST-001

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5

Literatures (Medical) associated with AST-001

01 Mar 2001·Antimicrobial Agents and ChemotherapyQ2 · MEDICINE

Molecular and Biochemical Analysis of AST-1, a Class A β-Lactamase from Nocardia asteroides Sensu Stricto

Q2 · MEDICINE

Article

Author: Boiron, Patrick ; Naas, Thierry ; Labia, Roger ; Poirel, Laurent ; Laurent, Frederic ; Nordmann, Patrice

ABSTRACT A β-lactamase gene was cloned from a Nocardia asteroides sensu stricto clinical isolate. A recombinant plasmid, pAST-1, expressed the β-lactamase AST-1 in Escherichia coli JM109. Its pI was 4.8, and its relative molecular mass was 31 kDa. E. coli JM109(pAST-1) was resistant to penicillins and narrow-spectrum cephalosporins. The β-lactamase AST-1 had a restricted hydrolytic activity spectrum. Its activity was partially inhibited by clavulanic acid but not by sulbactam and tazobactam. AST-1 is an Ambler class A β-lactamase sharing 65% amino acid identity with β-lactamase FAR-1, the most closely related enzyme.

01 Aug 1992·Experientia

Phosphoramidon enhances allatostatin-mediated inhibition of juvenile hormone biosynthesis in the corpora allta of the cockroach,Diploptera punctata

Article

Author: C. G. Yu ; S. S. Tobe ; K. J. Yagi

Use of enkephalinase inhibitor phosphoramidon in the in vitro radiochemical assay for juvenile hormone biosynthesis enhanced allatostatin-mediated inhibition of hormone production by corpora allata of the cockroach, Diploptera punctata. Significant increases in inhibition in day 2 virgin female CA by AST 1 (at 10(-7) M) and AST 4 (10(-8)-10(-7) M) were observed in the presence of phosphoramidon (10(-5) M or greater). No significant increase in inhibition were seen in CA from day 6 mated females with AST 4 (10(-9)-10(-7) M) and phosphoramidon combined. Phosphoramidon alone had no effect on JH biosynthesis. Analysis of allatostatin content of the CA, as determined by ELISA, revealed that addition of phosphoramidon to the medium increased the endogenous allatostatin content in CA of virgin and mated females. The similarity in primary structure between allatostatins and enkephalin-like peptides and their similar distribution makes it probable that phosphoramidon acts by preventing breakdown of allatostatins within the CA.

West Indian Medical JournalQ4 · MEDICINE

Demonstration of antihistamine properties with AST-1: a bioactive extract from garden slugs (Diplosolenodes occidentalis)

Q4 · MEDICINE

Article

Author: Reese, P ; Singh, P ; Jacob, A ; Simon, O

Parched and ground whole garden slugs are claimed in rural Jamaican folklore practices to have useful effects in the treatment of bronchial asthma. Since this claim may be associated with respiratory dysfunction due to histamine from allergic sensitization, the authors investigated the effects of a semi-pure alcoholic extract (AST-1) on histamine-induced contraction of the guinea pig in vitro tracheal muscle preparation and cutaneous allergic responses in ovalbumin sensitized guinea pigs. Chemical analysis of AST-1 by column chromatography and thin layer chromatography indicated two compounds in the composition, but the molecular structures were not determined Pharmacological evaluation of AST-1 produced a concentration-dependent inhibition of histamine-induced contraction of the guinea pig tracheal muscle preparation. AST-1 also inhibited contraction of the tracheal muscle produced by selective H1 receptor stimulation with HTMT dimaleate. H2 receptors were not involved, as indicated by the absence of contraction with dimaprit hydrochloride, a selective H2 agonist. Also, in ovalbumin sensitized guinea pigs, AST-1 and diphenhydramine, a selective H1 antagonist, inhibited the cutaneous responses due to intradermal injection of histamine and ovalbumin. These results suggest that AST-1 has H1 anti-histamine properties which can inhibit histamine-induced tracheobronchial muscle contraction and cutaneous responses due to allergy.

100 Deals associated with AST-001

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 2	CN	Ascentawits Pharmaceuticals Ltd.Startup	29 Apr 2022
Advanced Malignant Solid Neoplasm	Phase 1	CN	Ascentawits Pharmaceuticals Ltd.Startup	01 Jul 2022
Colonic Cancer	Phase 1	CN	Ascentawits Pharmaceuticals Ltd.Startup	01 Jul 2022
Hepatocellular Carcinoma	Phase 1	CN	Ascentawits Pharmaceuticals Ltd.Startup	01 Jul 2022
Non-Small Cell Lung Cancer	Phase 1	CN	Ascentawits Pharmaceuticals Ltd.Startup	01 Jul 2022
Pancreatic Cancer	Phase 1	CN	Ascentawits Pharmaceuticals Ltd.Startup	01 Jul 2022
Prostatic Cancer	Phase 1	CN	Ascentawits Pharmaceuticals Ltd.Startup	01 Jul 2022
Rectal Cancer	Phase 1	CN	Ascentawits Pharmaceuticals Ltd.Startup	01 Jul 2022
Renal Cell Carcinoma	Phase 1	CN	Ascentawits Pharmaceuticals Ltd.Startup	01 Jul 2022
Lung Cancer with Brain Metastasis	Phase 1	CN	Ascentawits Pharmaceuticals Ltd.Startup	30 Jan 2022