myelosuppression

PTC299 ((4-chlorophenyl) (1S)-6-chloro-1-(4-methoxyphenyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-2-carboxylate) is an orally active inhibitor of VEGFA mRNA translation and selectively inhibits VEGF protein synthesis at the post-transcriptional level. PTC299 is also a potent inhibitor of dihydrolactate dehydrogenase (DHODH).

Cyclophosphamide hydrate is a synthetic alkylating agent structurally related to nitrogen mustards, with antitumor and immunosuppressive activities. It is widely used in the treatment of various cancers and is also commonly employed to induce animal models of premature ovarian failure, myelosuppression, cystitis, and myocarditis.

Panaxatriol (Panaxtriol) can relieve myelosuppression induced by radiation injury.

Contezolid acefosamil sodium (MRX-4) is a novel orally active oxazolidinone antibiotic under investigation for the treatment of complicated skin and soft tissue infections (cSSTI) caused by drug-resistant Gram-positive bacteria. It possesses strong efficacy against these pathogens while significantly minimizing the risks of myelosuppression and monoamine oxidase inhibition (MAOI) [1][2].

Mitobronitol (Myelobromol; DBM) is a brominated analog of mannitol and an anticancer agent classified as an alkylating agent. Mitobronitol exhibits myelosuppressive effects, significantly reducing the risk of several complications in allogeneic bone marrow transplantation for accelerated chronic granulocytic leukemia [1] [2].

PC-046 is a potent tubulin-binding agent, which was originally identified for development based on selective activity in deleted in pancreas cancer locus 4 (DPC4 SMAD4) deficient tumors. PC-046 has growth inhibitory activity in a variety of tumor types in vitro, and efficacy in SCID mice was shown in human tumor xenografts of MV-4-11 acute myeloid leukemia, MM.1S multiple myeloma, and DU-145 prostate cancer. Pharmacokinetic studies demonstrated relatively high oral bioavailability (71 %) with distribution to both plasma and bone marrow. No myelosuppression was seen in non-tumor bearing SCID mice given a single dose just under the acute lethal dose. The COMPARE algorithm in the NCI-60 cell line panel demonstrated that PC-046 closely correlated to other known tubulin destabilizing agents (correlation coefficients ≈0.7 for vincristine and vinblastine). Mechanism of action studies showed cell cycle arrest in metaphase and inhibition of tubulin polymerization. Overall, these studi......