Last update 01 Nov 2024

MST1R x Tubulin

Last update 01 Nov 2024

Basic Info

Related Targets

MST1RTubulin

Drugs associated with MST1R x Tubulin

Zt/g4-maytansinoid(Texas Tech Univeristy)

Target

MST1R x Tubulin

Mechanism

MST1R inhibitors [+1]

Active Org.-

Originator Org.

Texas Tech University

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MST1R x Tubulin

100 Translational Medicine associated with MST1R x Tubulin

0 Patents (Medical) associated with MST1R x Tubulin

Literatures (Medical) associated with MST1R x Tubulin

01 May 2013·Molecular Cancer TherapeuticsQ2 · MEDICINE

Small-Molecule Inhibitor BMS-777607 Induces Breast Cancer Cell Polyploidy with Increased Resistance to Cytotoxic Chemotherapy Agents

Q2 · MEDICINE

Article

Author: Zhou, Yong-Qing ; Zeng, Jun-Ying ; Zhuang, Chun-Mei ; Zhang, Ruiwen ; Yao, Hang-Ping ; Hu, Xing ; Sharma, Sharad ; Wang, Ming-Hai

AbstractThe RON receptor tyrosine kinase is a therapeutic target for cancer treatment. Here, we report therapeutic effect and phenotypic change of breast cancer cells in response to BMS-777607, a RON tyrosine kinase inhibitor. Treatment of breast cancer cells with BMS-777607 at therapeutic doses inhibited cancerous clonogenic growth but had only minimal effect on cell apoptosis. Significantly, BMS-777607 induced extensive polyploidy with multiple sets of chromosomes in cancer cells. This effect is independent of RON expression. Knockdown of RON in T-47D and ZR-75-1 cells by specific siRNA did not prevent polyploid formation. Immunofluorescent analysis of α-tubulin and γ-tubulin expression in polyploid cells revealed that BMS-777607 disrupts bipolar spindle formation and causes multipolar-like microtubule assembly. Also, both metaphase equatorial alignment and chromosomal segregation were absent in polyploid cells. These results suggest that cellular mitosis arrests at prophase/pro-metaphase and fails to undergo cytokinesis. By analyzing kinase-inhibitory profiles, aurora kinase B was identified as the target molecule inhibited by BMS-777607. In BMS-777607–treated cells, aurora kinase B was inhibited followed by protein degradation. Moreover, BMS-777607 inhibited Ser10 phosphorylation of histone H3, a substrate of aurora kinase B. Chemosensitivity analysis indicated the resistance of polyploid cells toward chemotherapeutics. Treatment with doxorubicin, bleomycin, methotrexate, and paclitaxel significantly increased cellular IC50 values. These findings highlight the theory that BMS-777607 acts as a multikinase inhibitor at therapeutic doses and is capable of inducing polyploidy by inhibiting aurora kinase B. Increased resistance of polyploid cells to cytotoxic chemotherapeutics could have a negative impact on targeted cancer therapy using BMS-777607. Mol Cancer Ther; 12(5); 725–36. ©2013 AACR.

01 Jul 1998·Bone marrow transplantationQ3 · MEDICINE

Effects of superantigenic stimulation on the cord blood alphabeta T cell repertoire.

Q3 · MEDICINE

Article

Author: Gelin, C ; Charron, D ; Toubert, A ; Garderet, L ; Chalumeau, N ; Douay, C ; Zilber, M T ; Mooney, N ; Dulphy, N

Umbilical cord blood (CB) constitutes a promising alternative to bone marrow for allogeneic transplantation and is most remarkable for the reduced severity of GVHD compared with bone marrow. We have shown that although naive the TCR beta-chain repertoire appears fully constituted at birth in terms of mean size of the complementarity-determining region 3 (CDR3) and of the usage of V and J gene segments. Its ability to respond to exogenous stimuli was tested with staphylococcal superantigens TSST-1 and SEA (toxin at 1 ng/ml for 4 days). The amount of TCR transcripts was quantified and the percentage of representation of each BV family was calculated. TSST-1 induced BV2 expansion in both adult and CB samples. SEA activation gave a more variable pattern among individuals (adults n = 6; CB n = 6). BV6, BV18, BV22 and BV24 were the most frequently expanded families. We did not observe notable differences in either the modification of the TCRBV repertoire or the kinetics of the response to SEA superantigen between adults and newborns. These data suggest that although naive, CB lymphocytes are as equally capable as adult lymphocytes of responding to superantigen stimulation.

15 Mar 1996·Journal of immunology (Baltimore, Md. : 1950)

Residues near the amino and carboxyl termini of staphylococcal enterotoxin E independently mediate TCR V beta-specific interactions.

Article

Author: Lamphear, J G ; Mollick, J A ; Rich, R R ; Reda, K B

Previous studies identified three COOH-terminal residues in staphylococcal enterotoxin E (SEE; Asp200, Pro206, and Asp207) that in part mediate TCR V beta recognition. We have identified an additional three residues near the NH2-terminus of SEE (Arg20, Asn21, and Ser24 that are needed in conjunction with these COOH-terminal residues to fully restore native levels of V beta-specific T cell proliferation. A staphylococcal enterotoxin A SEA-SEE hybrid molecule containing the NH2-terminal V beta determinants of SEE to activate alone exhibited V beta specificities of both SEA and SEE, indicating that these residues of SEE independently contribute to V beta recognition and do not obscure the native V beta determinants of SEA. These findings suggest that the ability of SEE to activate certain V beta-specific T cell subsets may result from multiple interactions with a single TCR beta-chain or perhaps by cross-linking two TCR. High affinity binding to HLA-DR1, a property of native SEA, was not altered in the SEA-SEE hybrid enterotoxins containing amino acid substitutions in regions 20 to 24 and 200 to 207, indicating that residues comprising the V beta determinants of SEE are separate from residues that contribute to HLA-DR1 binding affinity. Computer models of the predicted structure of SEE revealed that the V beta determinants of SEE are located on two adjacent solvent-exposed loops. Thus, the residues of SEE that mediate V beta recognition may coalesce to form a TCR binding site with specificities for multiple TCR beta-chains.

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