• Kronos Bio's lead investigational therapy is entospletinib, a selective inhibitor targeting spleen tyrosine kinase (SYK) in development for the frontline treatment of NPM1-mutated acute myeloid leukemia (AML). (biospace.com)
  • The company is also developing KB-0742, an oral inhibitor of cyclin dependent kinase 9 (CDK9), for the treatment of MYC-amplified solid tumors. (biospace.com)
  • Voruciclib - Oral cyclin-dependent kinase 9 (CDK9) inhibitor for the treatment of B-cell malignancies and acute myeloid leukemia, as well as solid tumors. (bentoncourier.com)
  • Voruciclib is an orally administered Cyclin-dependent kinase 9 ( CDK9 ) inhibitor being clinically investigated for hematological malignancies. (bentoncourier.com)
  • The Company's product candidates, galinpepimut-S (GPS), a peptide immunotherapy directed against the Wilms tumor 1 (WT1), antigen, and GFH009, a selective small molecule cyclin-dependent kinase 9 (CDK9), inhibitor. (stockhouse.com)
  • The Company is also developing GFH009, a small molecule, selective CDK9 inhibitor, which is licensed from GenFleet Therapeutics (Shanghai), Inc., for all therapeutic and diagnostic uses in the world outside of Greater China. (stockhouse.com)
  • Flavopiridol is a synthetic flavone that has been postulated to be an inhibitor of cyclin-dependent kinases (CDKs) (Schmerwitz et al. (researchsquare.com)
  • We continued to advance our three clinical programs this quarter and, in addition, presented preclinical data that support the development strategy for our internally discovered CDK9 inhibitor, KB-0742, at the AACR Annual Meeting," said Norbert Bischofberger, Ph.D., president and chief executive officer of Kronos Bio. (kronosbio.com)
  • During the first quarter, Kronos Bio opened additional sites for its Phase 1b/2 clinical trial of lanraplenib, the company's next generation spleen tyrosine kinase (SYK) inhibitor, in combination with gilteritinib in patients with FLT3-mutated acute myeloid leukemia (AML). (kronosbio.com)
  • At the American Association for Cancer Research (AACR) Annual Meeting 2022 in April, Kronos Bio presented preclinical data that add to growing evidence in support of the company's approach to the clinical development of KB-0742, its internally discovered, highly selective, oral cyclin dependent kinase 9 (CDK9) inhibitor. (kronosbio.com)
  • CDKs belong to a family of serine/threonine kinases that need to form heterodimeric complexes with cyclins to perform their functions. (oncotarget.com)
  • CDKs belong to a large family of STKs that are regulated by their cognate cyclins. (umbc.edu)
  • Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. (rcsb.org)
  • The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6. (rcsb.org)
  • 2006 ). Among the CDKs, flavopiridol has a preference for suppression of CDK9 (Krystof et al. (researchsquare.com)
  • Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9. (umbc.edu)
  • Serine/Threonine Kinases (STKs), Cyclin-Dependent protein Kinase 9 (CDK9) subfamily, catalytic (c) domain. (umbc.edu)
  • HIPKs belong to the CMGC group of serine/threonine kinases and are part of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. (nature.com)
  • C-terminally adjacent to the HID follows a proline, glutamate, serine, and threonine (PEST)-rich domain, mediating proteasomal degradation of these kinases. (nature.com)
  • Cdk9 also phosphorylates the serine 2 of the heptapeptide repeats (YSPTSPS) of the C-terminal domain (CTD) of RNAPII to enhance elongation of transcription. (biomedcentral.com)
  • Several cell cycle regulatory functions may be mediated by Pur-alpha binding to Cyclin/Cdk protein kinases, which phosphorylate proteins regulating cell cycle transition points. (wikipedia.org)
  • These cell cycle effects are consistent with an interaction between Pur-alpha and CDK, cell cycle-dependent protein kinases. (wikipedia.org)
  • The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. (umbc.edu)
  • CDK9 has important functions in cell cycle regulation, including the modulation of two therapeutic targets in cancer: myeloid leukemia cell differentiation protein ("MCL1") and the MYC proto-oncogene protein ("MYC") which regulates cell proliferation and growth. (bentoncourier.com)
  • Homeodomain-interacting protein kinases (HIPKs) belong to the CMGC kinase family and are closely related to dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs). (nature.com)
  • Homeodomain-interacting protein kinases (HIPKs) are an evolutionarily conserved kinase family comprising the members HIPK1, HIPK2, and HIPK3 in vertebrates, and, additionally, HIPK4 in mammals. (nature.com)
  • Most hematological malignancies are characterized by overexpression of certain cancer-promoting genes, such as MYC, MCL1 and cyclin D1. (oncotarget.com)
  • Preclinical studies in animal models have shown that CDK9 inhibitors suppress the transcription of these anti-apoptotic and pro-survival proteins, and suggest their potential synergism with other drugs. (oncotarget.com)
  • Continue preclinical evaluation of the role CDK9 in cMYC regulation in solid tumors expressing KRAS mutations to support potential clinical development as a treatment for solid tumors. (bentoncourier.com)
  • ras2G19V influences transcription of late G1 phase cyclins via a poorly understood step in which Cln3 inactivates the Whi5 transcriptional repressor. (bvsalud.org)
  • Here we describe the development of CKIα inhibitors, which co-target the transcriptional kinases CDK7 and CDK9, thereby augmenting CKIα-induced p53 activation and its anti-leukemic activity. (regenerativemedicine.net)
  • For the class II DYRK ortholog from D. melanogaster it was demonstrated that the critical tyrosine is cis -auto-phosphorylated by the nascent kinase in a transitory intermediate state during maturation at the ribosome 3 . (nature.com)
  • LL-CDK9-12 demonstrated the most potent and selective degradation ability, with DC50 values of 0.362â µM against CDK9 and 0.680â µM against cyclin T1. (bvsalud.org)
  • CDK9 inhibitors could play a role in future treatments of hematological diseases and could be a great ally when combined with other therapeutic approaches. (oncotarget.com)
  • CDK9 inhibitors are relatively new drugs that inhibit transcription of these anti-apoptotic and pro-survival proteins. (oncotarget.com)
  • 2018 ). Currently, CDK9 inhibitors are considered potential treatments for inflammatory diseases (Hou et al. (researchsquare.com)
  • We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. (regenerativemedicine.net)
  • We determined the crystal structures of HIPK3 and DYRK1A bound to abemaciclib, showing a similar binding mode to the hinge region of the kinase as observed for Cdk6. (nature.com)
  • We utilize hydrophobic tag (HyT) based small-molecule degraders induced degradation of cyclin T1 and its corresponding kinase partner CDK9. (bvsalud.org)
  • In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. (umbc.edu)
  • These kinases are involved in multiple processes within cells, including cell cycle, apoptosis, transcription and differentiation. (oncotarget.com)
  • Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. (bvsalud.org)
  • Direct modulation of the non-kinase functions of cyclin and CDK-cyclin complexes poses challenges. (bvsalud.org)
  • Dorsoventral (DV) patterning of the Drosophila embryo is initiated by a broad Dorsal (Dl) nuclear gradient, which is regulated by a conserved signaling pathway that includes the Toll receptor and Pelle kinase. (sdbonline.org)
  • The H3K4 methyltransferase SETD1A plays a crucial role in leukemia cell survival through its noncatalytic FLOS domain-mediated recruitment of cyclin K and regulation of DNA damage response genes. (bvsalud.org)
  • Finally, effects of FUS on HIV gene transcription are also exhibited genome wide, where FUS mainly occupies gene promoters at transcription starting sites, while its knockdown leads to an increase in AFF4 and Cdk9 occupancy on gene promoters of FUS affected genes. (biomedcentral.com)
  • In this review, we will summarize and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease. (bvsalud.org)
  • Furthermore, this analyses confirmed the positive roles of CDK9 and Yorkie in regulating Mad-dependent gene expression in vivo. (sdbonline.org)
  • Here, we found that ras2G19V inhibits a critical step in cell cycle entry, in which an early G1 phase cyclin induces transcription of late G1 phase cyclins. (bvsalud.org)
  • Thus, ras2G19V drives overexpression of the early G1 phase cyclin Cln3, yet Cln3 fails to induce normal transcription of late G1 phase cyclins, leading to delayed cell cycle entry and increased cell size. (bvsalud.org)
  • However, while the role of the super elongation complex (SEC) in enhancing transcription activation of HIV is well established, the function of SEC in modulating viral latency is less defined and its cell partners are yet to be identified. (biomedcentral.com)
  • In light of the determination we made with our global partner, Kyowa Kirin, to discontinue development of zandelisib outside of Japan after a recent meeting with FDA, we have had to make some tough decisions. (bentoncourier.com)
  • I also want to recognize the collaborative efforts of our partner, Kyowa Kirin, and sincerely thank all the healthcare providers and patients that contributed to zandelisib's development. (bentoncourier.com)
  • As a result, it plans to initiate a staggered workforce reduction, initially representing approximately 30% of the current workforce in connection with the wind down of the zandelisib development program outside of Japan, which costs are shared with Kyowa Kirin, our global development partner. (bentoncourier.com)
  • In this study, we identify a functional nuclear localization signal in and interaction partners of the FLOS domain. (bvsalud.org)
  • Hyperactive Ras also influences expression of G1 phase cyclins in mammalian cells, but the mechanisms remain unclear. (bvsalud.org)
  • In prostate cancer cells, LL-CDK9-12 showed enhanced anti-proliferative activity than its parental molecule SNS032 and LL-K9-3, the previous reported CDK9-cyclin T1 degrader. (bvsalud.org)
  • In this study we identify fused in sarcoma (FUS) as a partner of AFF4 in cells. (biomedcentral.com)
  • however, ras2G19V appears to influence late G1 phase cyclin expression via novel PKA-independent signaling mechanisms. (bvsalud.org)
  • Further analysis of Ras signaling in yeast could lead to discovery of new mechanisms by which Ras family members control expression of G1 phase cyclins. (bvsalud.org)
  • Within the HIPK family, HIPK1 and HIPK2 are the most closely related members, sharing about 93% sequence identity in their kinase domains, while HIPK3 is slightly less conserved with 87% identity. (nature.com)
  • These kinases are often overexpressed in different malignancies, making them potential targets for new drugs. (oncotarget.com)