Delving into the Latest Updates on Teplinovivint with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CLK2 x DYRK1A

Action

inhibitors

Mechanism

CLK2 inhibitors(CDC like kinase 2 inhibitors), DYRK1A inhibitors(Dual-specificity tyrosine-phosphorylation regulated kinase 1A inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [3]

Active Indication-

Inactive Indication

Colorectal CancerLiver CancerPancreatic Cancer+ [3]

Originator Organization

Biosplice Therapeutics, Inc.

Active Organization-

Inactive Organization

Biosplice Therapeutics, Inc.

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H26N6O2

InChIKeyYDPWZFPXWFTXNT-UHFFFAOYSA-N

CAS Registry1428064-91-8

This study is a single-center, randomized, single-blind, placebo-controlled, multiple ascending dose study of SM04755 solution applied topically once daily for 14 days to intact skin overlying the inner thigh of healthy subjects at an estimated body surface area (BSA) of 80 cm^2. Dosing cohorts will consist of 8 subjects who will be randomized 3:1 (SM04755:placebo).

Start Date03 Nov 2016

Sponsor / Collaborator

Biosplice Therapeutics, Inc.

100 Clinical Results associated with Teplinovivint

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100 Translational Medicine associated with Teplinovivint

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100 Patents (Medical) associated with Teplinovivint

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2

Literatures (Medical) associated with Teplinovivint

31 Dec 2022·Journal of Enzyme Inhibition and Medicinal ChemistryQ2 · MEDICINE

Angiogenesis and anti-leukaemia activity of novel indole derivatives as potent colchicine binding site inhibitors

Q2 · MEDICINE

ArticleOA

Author: Feng, Siqi ; Wang, Yuyang ; Huang, Tao ; Wang, Longfei ; Yao, Yongfang ; Cheng, Weyland ; Duan, Yongtao ; Yang, Longhua

The screened compound DYT-1 from our in-house library was taken as a lead (inhibiting tubulin polymerisation: IC₅₀=25.6 µM, anti-angiogenesis in Zebrafish: IC₅₀=38.4 µM, anti-proliferation against K562 and Jurkat: IC₅₀=6.2 and 7.9 µM, respectively). Further investigation of medicinal chemistry conditions yielded compound 29e (inhibiting tubulin polymerisation: IC₅₀=4.8 µM and anti-angiogenesis in Zebrafish: IC₅₀=3.6 µM) based on tubulin and zebrafish assays, which displayed noteworthily nanomolar potency against a variety of leukaemia cell lines (IC₅₀= 0.09-1.22 µM), especially K562 cells where apoptosis was induced. Molecular docking, molecular dynamics (MD) simulation, radioligand binding assay and cellular microtubule networks disruption results showed that 29e stably binds to the tubulin colchicine site. 29e significantly inhibited HUVEC tube formation, migration and invasion in vitro. Anti-angiogenesis in vivo was confirmed by zebrafish xenograft. 29e also prominently blocked K562 cell proliferation and metastasis in blood vessels and surrounding tissues of the zebrafish xenograft model. Together with promising physicochemical property and metabolic stability, 29e could be considered an effective anti-angiogenesis and -leukaemia drug candidate that binds to the tubulin colchicine site.

01 Sep 2021·Journal of Orthopaedic ResearchQ3 · MEDICINE

SM04755, a small‐molecule inhibitor of the Wnt pathway, as a potential topical treatment for tendinopathy

Q3 · MEDICINE

Article

Author: Deshmukh, Vishal ; Ghias, Abdullah ; O'Green, Alyssa L. ; Hood, John ; Yazici, Yusuf ; Ibanez, Maureen ; Barroga, Charlene ; KC, Sunil ; Hofilena, Brian ; Seo, Tim ; Kennedy, Sarah ; Dellamary, Luis ; Chiu, Kevin ; Tambiah, Jeyanesh ; Stewart, Joshua

AbstractThe Wnt pathway is upregulated in tendinopathy, affecting inflammation and tenocyte differentiation. Given its potential role in tendinopathy, this signaling pathway may be a relevant target for treatment. The current study examined the therapeutic potential of SM04755, a topical, small‐molecule Wnt pathway inhibitor, for the treatment of tendinopathy using in vitro assays and animal models. In vitro, SM04755 decreased Wnt pathway activity, induced tenocyte differentiation, and inhibited catabolic enzymes and pro‐inflammatory cytokines in human mesenchymal stem cells, rat tendon‐derived stem cells, and human peripheral blood mononuclear cells. Evaluation of the mechanism of action of SM04755 by biochemical profiling and computational modeling identified CDC‐like kinase 2 (CLK2) and dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A) as molecular targets. CLK and DYRK1A inhibition by siRNA knockdown or pharmacological inhibition induced tenocyte differentiation and reduced tenocyte catabolism. In vivo, topically applied SM04755 showed therapeutically relevant exposure in tendons with low systemic exposure and no detectable toxicity in rats. Moreover, SM04755 showed reduced tendon inflammation and evidence of tendon regeneration, decreased pain, and improved weight‐bearing function in rat collagenase‐induced tendinopathy models compared with vehicle control. Together, these data demonstrate that CLK2 and DYRK1A inhibition by SM04755 resulted in Wnt pathway inhibition, enhanced tenocyte differentiation and protection, and reduced inflammation. SM04755 has the potential to benefit symptoms and modify disease processes in tendinopathy.

100 Deals associated with Teplinovivint

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Tendinopathy	Phase 1	United States	Biosplice Therapeutics, Inc.	03 Nov 2016
Colorectal Cancer	Phase 1	United States	Biosplice Therapeutics, Inc.	19 Jun 2014
Liver Cancer	Phase 1	United States	Biosplice Therapeutics, Inc.	19 Jun 2014
Pancreatic Cancer	Phase 1	United States	Biosplice Therapeutics, Inc.	19 Jun 2014
Stomach Cancer	Phase 1	United States	Biosplice Therapeutics, Inc.	19 Jun 2014
Scleroderma, Systemic	Phase 1	United States	Biosplice Therapeutics, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EULAR2018	Not Applicable	Psoriasis	-	SM04755	(ajtdnihjgj) = blqceynmmx bocmbqpzfq (dbrvboyipk ) View more	Positive	13 Jun 2018
EULAR2018	Not Applicable	Psoriasis	-	Vehicle	(ajtdnihjgj) = dhpmvmpiuc bocmbqpzfq (dbrvboyipk ) View more	Positive	13 Jun 2018
DISCOVERY OF A SMALL MOLECULE WNT PATHWAY INHIBITOR (WCO_IOF_ESCEO2017)	Not Applicable	Tendinopathy	-	SM04755	(lgmdzxcaaf) = yodyrlwocn hygtqezzzl (slcznhyqdy )	Positive	24 Jul 2017
ACR2016	Not Applicable	Tendinopathy	-	SM04755	kzecmldtyj(iomphrjewe) = fjffmzbaaa hpgessdwmx (tddqvwtqcq )	Positive	14 Nov 2016