Delving into the Latest Updates on Uzansertib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

PIM1 inhibitors(Proto-oncogene serine/threonine-protein kinase Pim-1 inhibitors), PIM2 inhibitors(Serine/threonine-protein kinase pim-2 inhibitors), PIM3 inhibitors(Serine/threonine-protein kinase pim-3 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication-

Inactive Indication

Diffuse large B-cell lymphoma recurrentDiffuse large B-cell lymphoma refractorySolid tumor

Originator Organization

Incyte Corp.

Active Organization-

Inactive Organization

Incyte Corp.

Drug Highest PhaseDiscontinuedPhase 1/2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC26H26F3N5O3

InChIKeyPTORCEYGCGXHDH-OVMXCRKPSA-N

CAS Registry1620012-39-6

This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies. The study will be conducted in 4 parts. Part 1 (monotherapy dose escalation) will evaluate safety and determine the maximum tolerated dose of INCB053914 monotherapy and the recommended phase 2 dose(s) (a tolerated pharmacologically active dose that will be taken forward into the remaining parts of the study). Part 2 (monotherapy dose expansion) will further evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the recommended Phase 2 dose(s). Part 3 (combination dose finding) will evaluate safety of INCB053914 in combination with select standard of care (SOC) agents and will identify the optimal INCB053914 dose in combination with conventional SOC regimens to take forward into Part 4. Part 4 (combination dose expansion) will further evaluate the safety, efficacy and pharmacokinetics of the recommended Phase 2 dose combination(s).

Start Date29 Dec 2015

Sponsor / Collaborator

Incyte Corp.

100 Clinical Results associated with Uzansertib

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100 Translational Medicine associated with Uzansertib

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100 Patents (Medical) associated with Uzansertib

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4

Literatures (Medical) associated with Uzansertib

01 Sep 2023·Clinical lymphoma, myeloma & leukemia

Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies.

Article

Author: Fathi, Amir T ; Marando, Cindy ; Byrne, Michael ; Asch, Adam S ; Baer, Maria R ; Cheng, Lulu ; Savona, Michael R ; Donnellan, William ; Kuykendall, Andrew T ; Walker, Chris ; Zeidan, Amer M ; Zheng, Fred ; Patel, Manish R

BACKGROUNDThe Proviral Integration site of Moloney murine leukemia virus (PIM) kinases are implicated in tumorigenesis; the pan-PIM kinase inhibitor, INCB053914, demonstrated antitumor activity in hematologic malignancy preclinical models.PATIENTS AND METHODSThis phase 1/2 study evaluated oral INCB053914 alone or combined with standard-of-care agents for advanced hematologic malignancies (NCT02587598). In Parts 1/2 (monotherapy), patients (≥18 years) had acute leukemia, high-risk myelodysplastic syndrome (MDS), MDS/myeloproliferative neoplasm, myelofibrosis (MF), multiple myeloma, or lymphoproliferative neoplasms. In Parts 3/4 (combination therapy), patients had relapsed/refractory or newly diagnosed (≥65 years, unfit for intensive chemotherapy) acute myeloid leukemia (AML) or MF with suboptimal ruxolitinib response.RESULTSParts 1/2 (n = 58): 6 patients experienced dose-limiting toxicities (DLTs), most commonly aspartate aminotransferase/alanine aminotransferase-elevated (AST/ALT; each n = 4). Fifty-seven patients (98.3%) had treatment-emergent adverse events (TEAEs), most commonly ALT-elevated and fatigue (36.2% each); 48 (82.8%) had grade ≥3 TEAEs, most commonly anemia (31.0%); 8 (13.8%) had grade ≥3 ALT/AST-elevated TEAEs. Parts 3/4 (n = 39): for INCB053914 + cytarabine (AML; n = 6), 2 patients experienced DLTs (grade 3 maculopapular rash, n = 1; grade 3 ALT-elevated and grade 4 hypophosphatemia, n = 1); for INCB053914 + azacitidine (AML; n = 16), 1 patient experienced a DLT (grade 3 maculopapular rash). Two complete responses were observed (1 with incomplete count recovery). For INCB053914 + ruxolitinib (MF; n = 17), no DLTs occurred; 3 patients achieved best reduction of >25% spleen volume at week 12 or 24.CONCLUSIONINCB053914 was generally well tolerated as monotherapy and in combinations; TEAEs were most commonly ALT/AST-elevated. Limited responses were observed with combinations. Future studies are needed to identify rational, effective combination strategies.

01 Apr 2020·Fish & Shellfish ImmunologyQ2 · AGRICULTURAL & FORESTRY SCIENCE

RNA-Seq analysis reveals that spring viraemia of carp virus induces a broad spectrum of PIM kinases in zebrafish kidney that promote viral entry

Q2 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Pereiro, Patricia ; Valenzuela-Muñoz, Valentina ; Figueras, Antonio ; Gallardo-Escárate, Cristian ; Novoa, Beatriz ; Álvarez-Rodríguez, Margarita

PIM kinases are a family of serine/threonine protein kinases that potentiate the progression of the cell cycle and inhibit apoptosis. Because of this, they are considered to be proto-oncogenes, and they represent an interesting target for the development of anticancer drugs. In mammals, three PIM kinases exist (PIM-1, PIM-2 and PIM-3), and different inhibitors have been developed to block their activity. In addition to their involvement in cancer, some publications have reported that the PIM kinases have pro-viral activity, and different mechanisms where PIM kinases favour viral infections have been proposed. Zebrafish possess more than 300 Pim kinase members in their genome, and by using RNA-Seq analysis, we found a high number of Pim kinase genes that were significantly induced after infection with spring viraemia of carp virus (SVCV). Moreover, analysis of the miRNAs modulated by this infection revealed that some of them could be involved in the post-transcriptional regulation of Pim kinase abundance. To elucidate the potential role of the 16 overexpressed Pim kinases in the infectivity of SVCV, we used three different pan-PIM kinase inhibitors (SGI-1776, INCB053914 and AZD1208), and different experiments were conducted both in vitro and in vivo. We observed that the PIM kinase inhibitors had a protective effect against SVCV, indicating that, similar to what is observed in mammals, PIM kinases are beneficial for the virus in zebrafish. Moreover, zebrafish Pim kinases seem to facilitate viral entry into the host cells because when ZF4 cells were pre-incubated with the virus and then were treated with the inhibitors, the protective effect of the inhibitors was abrogated. Although more investigation is necessary, these results show that pan-PIM kinase inhibitors could serve as a useful treatment for preventing the spread of viral diseases.

26 Nov 2019·Blood AdvancesQ2 · MEDICINE

The pan-PIM inhibitor INCB053914 displays potent synergy in combination with ruxolitinib in models of MPN

Q2 · MEDICINE

Article

Author: Stubbs, Matthew C. ; Reuther, Gary W. ; Koblish, Holly K. ; Lambert-Showers, Que T. ; Pandey, Garima ; Amin, Narmin E. ; Epling-Burnette, Pearlie K. ; Zhang, Ling ; Mazzacurati, Lucia ; Collins, Robert J.

Key PointsINCB053914 and ruxolitinib synergize to induce apoptosis of JAK2V617F-driven cells and to inhibit neoplastic growth of primary MPN cells. INCB053914 antagonizes ruxolitinib persistence in an in vivo MPN model.

100 Deals associated with Uzansertib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse large B-cell lymphoma recurrent	Phase 2	US	Incyte Corp.	03 Dec 2018
Diffuse large B-cell lymphoma refractory	Phase 2	US	Incyte Corp.	03 Dec 2018
Solid tumor	Phase 2	US	Incyte Corp.	29 Dec 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02587598 (Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914, Pubmed \| Clin Lymphoma Myeloma Leuk)	Phase 1/2	Hematologic Neoplasms	-	INCB053914 alone	ekmqhfdcwt(yfnjrakdkf) = most commonly ALT/AST-elevated menlotzlep (nknbuzqkcq ) View more	Negative	01 Sep 2023
				INCB053914 + cytarabine
NCT02587598 (ASH2017) Manual	Phase 1/2	Hematologic Neoplasms	39	INCB053914 (TGA)	uwmdiasihv(cnjzhvgqsd) = junepjzkoi bzukzowhaa (pugzmffqqr )	Positive	07 Dec 2017
				INCB053914 (TGB)	uwmdiasihv(cnjzhvgqsd) = yojneoavkz bzukzowhaa (pugzmffqqr )