Heike I. Krupka

The evolution of cyclin dependent kinase inhibitors in the treatment of cancer

Komal L. Jhaveri, Howard A Burris rd, Timothy Anthony Yap, Erika Paige Hamilton et autres

Introduction: The cell cycle cyclin-dependent kinases (CDKs) play a critical role in controlling the transition between cell cycle phases, as well as cellular transcription. Aberrant CDK activation is common in cancer, and deregulation of the cell cycle a key hallmark of cancer. …

us (code pays fourni par la source)

Preliminary Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Subcutaneously (SC) Administered PF-06863135, a B-Cell Maturation Antigen (BCMA)-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Alexander M. Lesokhin, Moshe Yair Levy, Andrew Peter Dalovisio, Nizar Jacques Bahlis et autres

Introduction: PF-06863135 (PF-3135) is a full-length, humanized, bispecific monoclonal antibody (mAb, IgG2a) targeting BCMA, which is highly expressed on multiple myeloma cells, and CD3 expressed on T cells. Intravenous (IV) dosing of PF-3135 has been previously evaluated at 0.1 - 50 μg/kg …

us, ca (code pays fourni par la source)

Abstract 4557: BCMA-CD3 bispecific antibody PF-06863135: Preclinical rationale for therapeutic combinations

Katarzyna Karwacz, Andrea T. Hooper, Chao-Pei Betty Chang, Heike I. Krupka et autres

Abstract BCMA-CD3 bispecific antibody PF-06863135 is currently under evaluation in an ongoing Phase 1 clinical trial in relapsed/refractory (RR) multiple myeloma (MM) patients (NCT03269136). We showed previously that BCMA-CD3 bispecific has potent single agent activity in RR MM human bone marrow aspirates …

us (code pays fourni par la source)

Safety, Clinical Activity, Pharmacokinetics, and Pharmacodynamics from a Phase I Study of PF-06863135, a B-Cell Maturation Antigen (BCMA)-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Noopur S Raje, Andrzej J. Jakubowiak, Cristina Gasparetto, Robert Frank Cornell et autres

Introduction: PF-06863135 (PF-3135) is a bispecific, humanized, monoclonal antibody (mAb) consisting of BCMA- and CD3-targeting arms paired on an IgG2a backbone by hinge-mutation technology. PF-3135 binds BCMA+ myeloma cells and CD3+ T cells with affinities of 20 pM and ~40 nM, respectively …

us (code pays fourni par la source)

A Phase I, Open-Label Study to Evaluate the Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity of PF-06863135, a B-Cell Maturation Antigen/CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Advanced Multiple Myeloma

Alexander M. Lesokhin, Noopur S Raje, Cristina Gasparetto, Justine Walker et autres

Abstract Background: Despite a number of recent advances in the treatment of multiple myeloma (MM), the majority of patients are likely to relapse or become resistant to current treatment options. PF-06863135 (PF-3135) is a humanized immunoglobulin G (IgG) CD3 bispecific monoclonal antibody …

us (code pays fourni par la source)

Pharmacodynamic (PD) changes in tumors and peripheral blood T cell receptor (TCR) repertoire in a phase I study combining OX40 (PF-04518600) and 4-1BB (utomilumab) agonistic monoclonal antibodies (mAbs)

Omid Hamid, Siwen Hu‐Lieskovan, Willeke Ros, Adi Diab et autres

Background: PF-04518600 (PF-8600) and utomilumab (uto) are human IgG2 agonistic mAbs against the tumor necrosis factor superfamily receptors OX40 and 4-1BB, respectively. Both receptors play key roles in T cell survival, proliferation, and activation. PF-8600 has been shown to increase proliferation and …

us, nl, fr, jp (code pays fourni par la source)

A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors

Gentry Teng King, Keith D. Eaton, Brandon R. Beagle, Christopher J. Zopf et autres

us (code pays fourni par la source)

Abstract 2667: In vitro properties and pre-clinical activity of PF-06801591, a high-affinity engineered anti-human PD-1

Sawsan Youssef, Yasmina Noubia Abdiche, HoangKim T. Nguyen, Joyce Chou et autres

Abstract Monoclonal-antibody-based therapies targeting the immune checkpoint receptors have become the new standard of care in many cancers. Antibodies that specifically target programmed death receptor-1 (PD-1) or its cognate ligand, programmed death receptor ligand-1 (PD-L1), alone or in combination, have yielded clinical …

us (code pays fourni par la source)

Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent

Dean R. Artis, Jack J. Lin, Chao Zhang, Weiru Wang et autres

In a search for more effective anti-diabetic treatment, we used a process coupling low-affinity biochemical screening with high-throughput co-crystallography in the design of a series of compounds that selectively modulate the activities of all three peroxisome proliferator-activated receptors (PPARs), PPARalpha, PPARgamma, and …

us (code pays fourni par la source)

Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase

Weiru Wang, Adhirai Marimuthu, James Y. Tsai, Abhinav Kumar et autres

Protein kinases are a large family of cell signaling mediators undergoing intensive research to identify inhibitors or modulators useful for medicine. As one strategy, small-molecule compounds that bind the active site with high affinity can be used to inhibit the enzyme activity. …

Structural Characterization of autoinhibited c-Met kinase

W. Wang, Anushree Marimuthu, Jeng-Wen Tsai, Heike I. Krupka et autres

The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1

Weiru Wang, Chao Zhang, Adhirai Marimuthu, Heike I. Krupka et autres

Steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1) belong to the fushi tarazu factor 1 subfamily of nuclear receptors. SF-1 is an essential factor for sex determination during development and regulates adrenal and gonadal steroidogenesis in the adult, whereas LRH-1 is a …

us (code pays fourni par la source)