Delving into the Latest Updates on Dezapelisib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Dezapelisib (USAN)

+ [2]

Target

PI3Kδ

Action

inhibitors

Mechanism

PI3Kδ inhibitors(Phosphatidylinositol 3 kinase delta inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesInfectious Diseases+ [3]

Active Indication

Burkitt LymphomaWaldenstrom Macroglobulinemia

Inactive Indication

Refractory Hodgkin Lymphoma

Originator Organization

Incyte Corp.

Active Organization

Incyte Corp.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC20H16FN7OS

InChIKeyRSIWALKZYXPAGW-NSHDSACASA-N

CAS Registry1262440-25-4

The study will be conducted in three parts. Part 1 is a dose escalation phase to determine the maximum tolerated dose (MTD) of INCB040093, a PI3Kδ inhibitor, or a tolerated, pharmacologically active dose; Part 2 will evaluate the combination of INCB040093 and itacitinib (INCB039110), a JAK1 inhibitor, to determine the MTD of the combination or a tolerated dose that produces substantial pharmacologic inhibition of both targets; Part 3 will further evaluate the chosen doses of INCB040093 alone and in combination with itacitinib (INCB039110) in subjects with relapsed/refractory B-cell malignancies.

Start Date30 Jun 2013

Sponsor / Collaborator

Incyte Corp.

100 Clinical Results associated with Dezapelisib

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100 Translational Medicine associated with Dezapelisib

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100 Patents (Medical) associated with Dezapelisib

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4

Literatures (Medical) associated with Dezapelisib

14 Nov 2019·ACS Medicinal Chemistry LettersQ3 · MEDICINE

INCB050465 (Parsaclisib), a Novel Next-Generation Inhibitor of Phosphoinositide 3-Kinase Delta (PI3Kδ)

Q3 · MEDICINE

Article

Author: Shin, Niu ; Polam, Padmaja ; Scherle, Peggy ; He, Xin ; Diamond, Sharon ; Yue, Eddy W. ; Sparks, Richard B. ; Falahatpisheh, Nikoo ; Mei, Song ; Hall, Leslie ; Zhu, Wenyu ; Zhang, Ke ; Maduskuie, Thomas ; Glenn, Joseph ; Douty, Brent ; Koblish, Holly K. ; Li, Yanlong ; Wang, Kathy He ; Feldman, Patricia ; He, Chunhong ; Feng, Hao ; Katiyar, Kamna ; Metcalf, Brian ; Combs, Andrew P. ; Yeleswaram, Swamy ; Li, Yun-Long ; Li, Yu ; Covington, Maryanne ; Yao, Wenqing ; Wayland, Brian ; Xue, Chu-Biao

A medicinal chemistry effort focused on identifying a structurally diverse candidate for phosphoinositide 3-kinase delta (PI3Kδ) led to the discovery of clinical candidate INCB050465 (20, parsaclisib). The unique structure of 20 contains a pyrazolopyrimidine hinge-binder in place of a purine motif that is present in other PI3Kδ inhibitors, such as idelalisib (1), duvelisib (2), and INCB040093 (3, dezapelisib). Parsaclisib (20) is a potent and highly selective inhibitor of PI3Kδ with drug-like ADME properties that exhibited an excellent in vivo profile as demonstrated through pharmacokinetic studies in rats, dogs, and monkeys and through pharmacodynamic and efficacy studies in a mouse Pfeiffer xenograft model.

19 Jul 2018·BloodQ1 · MEDICINE

Phase 1 study of the PI3Kδ inhibitor INCB040093 ± JAK1 inhibitor itacitinib in relapsed/refractory B-cell lymphoma

Q1 · MEDICINE

Article

Author: Diefenbach, Catherine S. ; Scherle, Peggy ; Phillips, Tycel J. ; Sher, Taimur ; Barr, Paul M. ; Zhou, Li ; Johnston, Patrick ; Talpaz, Moshe ; Chen, Xuejun ; Forero-Torres, Andres ; Pulini, Jennifer

Key PointsINCB040093 was active across lymphoma subtypes, and the addition of itacitinib provided substantial activity in classic Hodgkin lymphoma. INCB040093 ± itacitinib had a manageable safety and tolerability profile; severe hepatic adverse effects were less common with the combination.

01 Jan 2018·The Journal of Pharmacology and Experimental Therapeutics

INCB040093 Is a Novel PI3Kδ Inhibitor for the Treatment of B Cell Lymphoid Malignancies

Article

Author: Favata, Margaret ; Hollis, Gregory ; Katiyar, Kamna ; Huber, Reid ; Rupar, Mark ; Leffet, Lynn ; Koblish, Holly ; Yeleswaram, Swamy ; Liu, Mike ; Burn, Timothy ; Newton, Robert ; Li, Jun ; Mei, Song ; Vaddi, Kris ; Wang, Kathy He ; Fridman, Jordan ; Shuey, Dana ; Soloviev, Maxim ; Scherle, Peggy ; Li, Yun-Long ; Li, Yanlong ; Yao, Wenqing ; Hall, Leslie ; Diamond, Sharon ; Covington, Maryanne ; Yang, Gengjie ; Combs, Andrew ; Wang, Qian ; Bowman, Kevin ; Shin, Niu ; He, Xin ; Rumberger, Beth

Phosphatidylinositol 3-kinase delta (PI3Kδ) is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδ small-molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies. In this study, we disclose the chemical structure and the preclinical activity of the compound. In biochemical assays, INCB040093 potently inhibits the PI3Kδ kinase, with 74- to >900-fold selectivity against other PI3K family members. In vitro and ex vivo studies using primary B cells, cell lines from B cell malignancies, and human whole blood show that INCB040093 inhibits PI3Kδ-mediated functions, including cell signaling and proliferation. INCB040093 has no significant effect on the growth of nonlymphoid cell lines and was less potent in assays that measure human T and natural killer cell proliferation and neutrophil and monocyte functions, suggesting that the impact of INCB040093 on the human immune system will likely be restricted to B cells. INCB040093 inhibits the production of macrophage-inflammatory protein-1β (MIP-1beta) and tumor necrosis factor-β (TNF-beta) from a B cell line, suggesting a potential effect on the tumor microenvironment. In vivo, INCB040093 demonstrates single-agent activity in inhibiting tumor growth and potentiates the antitumor growth effect of the clinically relevant chemotherapeutic agent, bendamustine, in the Pfeiffer cell xenograft model of non-Hodgkin's lymphoma. INCB040093 has a favorable exposure profile in rats and an acceptable safety margin in rats and dogs. Taken together, data presented in this report support the potential utility of orally administered INCB040093 in the treatment of B cell malignancies.

100 Deals associated with Dezapelisib

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External Link

KEGG	Wiki	ATC	Drug Bank
D10924	-	-	DB16137

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Burkitt Lymphoma	Phase 1	United States	Incyte Corp.	30 Jun 2013
Waldenstrom Macroglobulinemia	Phase 1	United States	Incyte Corp.	30 Jun 2013
Refractory Hodgkin Lymphoma	Preclinical	-	Incyte Corp.	01 Jun 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01905813 (Pubmed \| Circulation \| Blood) Manual	Phase 1	B-cell lymphoma refractory	121	INCB040093	(ksotqwtrwg) = The most common serious adverse events with monotherapy were pneumonia (n = 5) and pyrexia (n = 4), and with combination Pneumocystis jiroveci pneumonia (n = 5), pneumonia (unrelated to P jiroveci; n = 5), and pyrexia (n = 4). debrykgxqe (edjdavvlfv )	Positive	19 Jul 2018
				INCB040093+itacitinib
ICML2015	Phase 1	B-Cell Malignant Neoplasm	83	INCB040093 monotherapy	txfggklnrp(liybxsmlxu) = 28% tyhflzycsy (opbllosnhh ) View more	Positive	09 Jun 2015
				INCB040093+INCB039110 combination therapy
NCT01905813 (ASCO2015)	Phase 1	Relapsing classical Hodgkin lymphoma	17	INCB040093	(yeokrktebs) = 41% qoyyhxoeal (oklccavhyx ) View more	-	20 May 2015
				INCB040093 + INCB039110