Delving into the Latest Updates on PRN-371 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

JAK3

Mechanism

JAK3 inhibitors(Tyrosine-protein kinase JAK3 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication-

Inactive Indication

NK-cell lymphomaT-Cell Lymphoma

Originator Organization

Principia Biopharma, Inc.

Active Organization-

Inactive Organization

National Cancer Centre of Singapore Pte Ltd.

Principia Biopharma, Inc.

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC20H21N5O2

InChIKeyRGYYZLGXRYSDRO-UHFFFAOYSA-N

CAS Registry1610974-55-4

Author: Teh, B T ; Song, T L L ; Hill, R J ; Yeoh, K W ; Chia, B K H ; Tan, J ; Bradshaw, J M ; Rajasegaran, V ; Pang, W L ; Lim, J Q ; Xia, X J ; Huang, D ; Ng, C C Y ; Nairismägi, M -L ; Kang, T B ; Wijaya, G C ; Tang, Q Q ; Bisconte, A ; Ong, C K ; Yao, X S ; Laurensia, Y ; Lim, S T ; Tang, T ; Li, Z M ; Gerritsen, M E

Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. To improve the therapeutic efficacy of JAK3 inhibition in NKTL, we have developed a highly selective and durable JAK3 inhibitor PRN371 that potently inhibits JAK3 activity over the other JAK family members JAK1, JAK2, and TYK2. PRN371 effectively suppresses NKTL cell proliferation and induces apoptosis through abrogation of the JAK3-STAT signaling. Moreover, the activity of PRN371 has a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. These findings provide a novel therapeutic approach for the treatment of NKTL.

100 Deals associated with PRN-371

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
NK-cell lymphoma	Preclinical	US	Principia Biopharma, Inc.	30 Apr 2018
NK-cell lymphoma	Preclinical	US	National Cancer Centre of Singapore Pte Ltd.	30 Apr 2018
T-Cell Lymphoma	Preclinical	US	Principia Biopharma, Inc.	30 Apr 2018
T-Cell Lymphoma	Preclinical	US	National Cancer Centre of Singapore Pte Ltd.	30 Apr 2018