Hamish Wright

Abstract 4514: Development and validation of a CyTOF assay for measuring phosphoproteins in AML blast cell populations in whole blood from AML patients.

Steven Robert Pirie-Shepherd, Crystal Tarrago, Wenxin Zheng, Sen Zhang et autres

Abstract CDC7 (Cell Division Cycle 7-related protein kinase), also known as DBF4-dependent kinase (DDK), is a critical serine/threonine cell cycle protein kinase indispensable for maintaining DNA replication fork progression and stability, particularly under conditions of replication stress. CDC7 activates fork protection and …

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Sgr-2921, a Potent CDC7 Inhibitor, Demonstrates Significant Anti-Leukemic Responses in Patient-Derived AML Models Representing Difficult-to-Treat Disease

Hooman Izadi, Hui Wang, Christian Atsriku, Zef Konst et autres

Introduction: Elevated replication stress (RS) is a common feature of many highly proliferative cancers including AML. CDC7 has been shown to activate key components of the RS response, including ATR, and the BRCA1 and cohesin complexes, thereby mitigating accumulation of DNA damage …

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PB2349: A PHASE 1, OPEN-LABEL, MULTICENTER, DOSE-ESCALATION STUDY OF SGR-1505 AS MONOTHERAPY IN SUBJECTS WITH MATURE B-CELL MALIGNANCIES

Adam J. Olszewski, David Kahn, Byong Kwon Yoo, Zhe Nie et autres

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a component of the MALT1-BCL10-CARD11 complex downstream from the Bruton Tyrosine Kinase (BTK) on the B-cell receptor signaling pathway. MALT1 is a key mediator of …

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SGR‐1505‐101: A PHASE 1, OPEN‐LABEL, MULTICENTER, DOSE‐ESCALATION STUDY OF SGR‐1505 AS MONOTHERAPY IN SUBJECTS WITH MATURE B‐CELL MALIGNANCIES

Adam J. Olszewski, DOUGLAS G. KAHN, Byunggil Yoo, Zhe Nie et autres

Background: MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a component of the MALT1-BCL10-CARD11 complex downstream from the Bruton Tyrosine Kinase (BTK) on the B-cell receptor signaling pathway. MALT1 is a key mediator of the nuclear factor kappa B (NF-κB) signaling, …

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Inhibition of CDC7 with Sgr-2921 in AML Models Results in Enhanced DNA Damage and Anti-Leukemic Activity As Monotherapy and in Combination with Standard of Care Agents

Lyuben M. Tsvetkov, Janét Pittsenbarger, Christian Atsriku, Paul Devine et autres

Introduction: CDC7 is a protein kinase that is active during the S-phase of the cell cycle. CDC7 plays a critical role in the replication stress response by phosphorylation and activation of the BRCA1 and Cohesin complexes, which protect and restart stalled replication …

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Abstract 2570: Discovery of potent, selective, and orally available WEE1 inhibitors that demonstrate increased DNA damage and mitosis in tumor cells leading to tumor regression in vivo

Shaoxian Sun, Sarah Silvergleid, Aleksey I. Gerasyuto, Jiashi Wang et autres

Abstract WEE1 inhibits the activation of both CDK1 and CDK2 through phosphorylation of Tyr15, allowing DNA damage repair before entering mitosis, thereby regulating the cell cycle in S and G2/M phases. Inhibition of WEE1 could result in premature progression through the G2/M …

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Characterization of Potent Paracaspase MALT1 Inhibitors for Hematological Malignancies

Wu Yin, Zhe Nie, Karen H. Dingley, Michael Trzoss et autres

Abstract Introduction: MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a key mediator of the NF-κB signaling pathway, the main driver of a subset of B-cell lymphomas and functions by forming a complex with CARMA1 and BCL10 to mediate antigen receptor-induced …

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Abstract 1277: Discovery of novel CDC7 inhibitors that disrupt cell cycle dynamics and show anti-proliferative effects in cancer cells

Lyuben M. Tsvetkov, Adam Levinson, Xianhai Huang, Sayan Mondal et autres

Abstract Introduction: CDC7 is a serine/threonine protein kinase that phosphorylates the MCM2-7 helicase complex, a required step in DNA replication initiation. CDC7 has emerged as an attractive target for cancer treatment because of high expression in a number of tumors (e.g. ovarian, …

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Abstract 1338: Discovery of novel, potent USP7 inhibitors that upregulate p53 leading to anti-proliferative effects in cancer cells

Alan S. Futran, Tao Lu, Katherine Amberg-Johnson, Xiaoxiao Yang et autres

Abstract Introduction: Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that regulates several proteins involved in cell cycle, DNA repair, genomic stability, and epigenetics and has been implicated in cancer progression. A key substrate of USP7 is MDM2, the oncogenic E3 ubiquitin ligase …

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Identification of Potent Paracaspase MALT1 Inhibitors for Hematological Malignancies

Wu Yin, Zhe Nie, Andrew Placzek, Michael Trzoss et autres

Introduction: MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), was identified as a translocation protein fused with cIAP2 in mucosa-associated lymphoid tissue (MALT) B cell lymphomas. MALT1, a key mediator of NF-κB signaling and the main driver of a subset of B-cell …

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Bioequivalence of alendronate and vitamin D 3 in an alendronate/vitamin D 3 combination tablet (1053.2)

Geng‐Chang Yeh, Kevin D. Brown, Ramon Mols, Eric Woolf et autres

FOSAMAX® PLUS D is a once‐weekly alendronate (ALN) 70‐mg / vitamin D 3 (vit‐D 3 ) 5600 IU combination tablet developed by Merck & Co., Inc. A single‐dose, open‐label, randomized, 2‐period, crossover study was conducted to test bioequivalence between FOSAMAX® PLUS D …

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The Acyclic CB1R Inverse Agonist Taranabant Mediates Weight Loss by Increasing Energy Expenditure and Decreasing Caloric Intake

Carol Addy, Hamish Wright, Koen Van Laere, Ira Gantz et autres

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