Delving into the Latest Updates on SKI-G-801 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Denfivontinib

+ [1]

Target

FLT3

Mechanism

FLT3 inhibitors(Tyrosine-protein kinase receptor FLT3 inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Advanced Malignant Solid Neoplasm

Inactive Indication

Refractory acute myeloid leukemiaRelapsing acute myeloid leukemia

Originator Organization

Oscotec, Inc.

Active Organization

Oscotec, Inc.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC25H25BrN6O2

InChIKeySXWMIXPJPNCXQQ-UHFFFAOYSA-N

CAS Registry1457983-28-6

View All Structures (2)

This Phase I study is designed to assess the safety, tolerability, pharmacokinetics and anti-tumor effect of increasing doses of study drug SKI-G-801 in patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are unresponsive to currently available therapies. Eligible participants will receive cycles of treatment involving IV infusion of SKI-G-801 daily for 14 days followed by 14 days off. Treatment cycles will be repeated until progressive disease or unacceptable toxicity.

Start Date23 Feb 2018

Sponsor / Collaborator

Oscotec, Inc.

[+1]

100 Clinical Results associated with SKI-G-801

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100 Translational Medicine associated with SKI-G-801

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100 Patents (Medical) associated with SKI-G-801

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5

Literatures (Medical) associated with SKI-G-801

01 Jan 2022·Clinical & Translational ImmunologyQ3 · MEDICINE

SKI‐G‐801, an AXL kinase inhibitor, blocks metastasis through inducing anti‐tumor immune responses and potentiates anti‐PD‐1 therapy in mouse cancer models

Q3 · MEDICINE

ArticleOA

Author: Ahn, Beung‐Chul ; Yun, Jiyeon ; Jo, Ha Ni ; Kim, Sung Eun ; Kim, Jung‐Ho ; Kim, Jae Hwan ; Cho, Jae Seok ; Lee, Hee Kyu ; Synn, Chun‐Bong ; Pyo, Kyoung‐Ho ; Kim, Hye Ryun ; Lee, Ji Min ; Lim, Sangbin ; Kim, Do Hee ; Lim, Sun Min ; Lee, You Won ; Lee, Seul ; Cho, Byoung Chul ; Kim, Min‐Hwan ; Park, Sungho ; Yang, San‐Duk ; Lee, Sung Sook ; Lee, Wongeun ; Lee, Eun Ji ; Heo, Seong Gu ; Choi, Yewon ; Byeon, Youngseon ; Yun, Mi Ran ; Hong, Min Hee ; Park, Chae‐Won ; Choi, Hunmi ; Kim, Dong Kwon ; Kim, Young Seob ; Kim, Chang Gon

AbstractObjectivesAXL‐mediated activation of aberrant tyrosine kinase drives various oncogenic processes and facilitates an immunosuppressive microenvironment. We evaluated the anti‐tumor and anti‐metastatic activities of SKI‐G‐801, a small‐molecule inhibitor of AXL, alone and in combination with anti‐PD‐1 therapy.MethodsIn vitro pAXL inhibition by SKI‐G‐801 was performed in both human and mouse cancer cell lines. Immunocompetent mouse models of tumor were established to measure anti‐metastatic potential of SKI‐G‐801. Furthermore, SKI‐G‐801, anti‐PD‐1 or their combination was administered as an adjuvant or neoadjuvant in the 4T1 tumor model to assess their potential for clinical application.ResultsSKI‐G‐801 robustly inhibited pAXL expression in various cell lines. SKI‐G‐801 alone or in combination with anti‐PD‐1 potently inhibited metastasis in B16F10 melanoma, CT26 colon and 4T1 breast models. SKI‐G‐801 inhibited the growth of B16F10 and 4T1 tumor‐bearing mice but not immune‐deficient mice. An antibody depletion assay revealed that CD8+ T cells significantly contributed to SKI‐G‐801‐mediated survival. Anti‐PD‐1 and combination group were observed the increased CD8+Ki67+ and effector T cells and M1 macrophage and decreased M2 macrophage, and granulocytic myeloid‐derived suppressor cell (G‐MDSC) compared to the control group. The neoadjuvant combination of SKI‐G‐801 and anti‐PD‐1 therapy achieved superior survival benefits by inducing more profound T‐cell responses in the 4T1 syngeneic mouse model.ConclusionSKI‐G‐801 significantly suppressed tumor metastasis and growth by enhancing anti‐tumor immune responses. Our results suggest that SKI‐G‐801 has the potential to overcome anti‐PD‐1 therapy resistance and allow more patients to benefit from anti‐PD‐1 therapy.

01 Dec 2018·Journal of Hematology & OncologyQ1 · MEDICINE

FLT3 inhibitors in acute myeloid leukemia

Q1 · MEDICINE

ReviewOA

Author: Li, Chuntuan ; Zhu, Xiongpeng ; Wu, Mei

FLT3 mutations are one of the most common findings in acute myeloid leukemia (AML). FLT3 inhibitors have been in active clinical development. Midostaurin as the first-in-class FLT3 inhibitor has been approved for treatment of patients with FLT3-mutated AML. In this review, we summarized the preclinical and clinical studies on new FLT3 inhibitors, including sorafenib, lestaurtinib, sunitinib, tandutinib, quizartinib, midostaurin, gilteritinib, crenolanib, cabozantinib, Sel24-B489, G-749, AMG 925, TTT-3002, and FF-10101. New generation FLT3 inhibitors and combination therapies may overcome resistance to first-generation agents.

03 Apr 2014·BloodQ1 · MEDICINE

G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia

Q1 · MEDICINE

Article

Author: Kim, Hong Woo ; Lee, Jaekyoo ; Park, Sung Ho ; Koh, Jong Sung ; Lee, In Yong ; Kim, Jung Keun ; Lee, Jungmi ; Song, Ho-Juhn ; Lee, Sang Yeop ; Hwang, Haejun ; Kim, Jung-Ho ; Kim, Se Won ; Choi, Jang-Sik ; Lee, Hee Kyu ; Jung, Dong Sik ; Cools, Jan

Key PointsA novel inhibitor G-749 is very potent against FLT3 kinase mutants including D835Y and ITD/F691L that confer resistance to PKC412 and AC220. G-749 shows several desirable characteristics to overcome other drug resistances conferred by patient plasma, FLT3 ligand, and stromal cells.

100 Deals associated with SKI-G-801

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	KR	Oscotec, Inc.	25 Jan 2022
Refractory acute myeloid leukemia	Discovery	US	Oscotec, Inc.	23 Feb 2018
Relapsing acute myeloid leukemia	Discovery	US	Oscotec, Inc.	23 Feb 2018