cml

Dasatinib (BMS-354825) is an orally active, ATP-competitive tyrosine kinase inhibitor that targets Src and Bcr-Abl (Ki=16 30 pM), with antitumor activity, used in the treatment of leukemia and lymphoma.

Dasatinib monohydrate (BMS-354825 Monohydrate) is an orally bioavailable synthetic small molecule-inhibitor of SRC-family protein-tyrosine kinases. Dasatinib monohydrate binds to and inhibits the growth-promoting activities of these kinases. Apparently, because of its less stringent binding affinity for the BCR-ABL kinase, Dasatinib monohydrate has been shown to overcome the resistance to imatinib of chronic myeloid leukemia (CML) cells harboring BCR-ABL kinase domain point mutations.

Nε-(1-Carboxymethyl)-L-lysine (CML), an advanced glycation end product (AGE), is formed through the oxidative modification of glycated proteins under conditions of oxidative stress.1,2,3 Its levels escalate with age, diabetes, cancer, vascular diseases, and various pathologies associated with oxidative stress.1,4,5 CML interacts with the membrane-bound receptor for AGEs (RAGE), initiating signaling via MAPKs and NF-κB pathways. Conversely, a truncated version of RAGE generates a soluble protein that sequesters CML, thereby diminishing this signaling.6,7

CMLD010509 (SDS-1-021) is a highly selective inhibitor of the oncogenic translation program that supports multiple myeloma (MM), targeting key oncoproteins such as MDM2, CCND1, MYC, MAF, and MCL-1.

CMLD012072 is a potent eukaryotic initiation factor 4A (eIF4A) inhibitor with potent anti-neoplastic activity. It can induce RNA clamping of eIF4A1 and eIF4A2.

CMLD012073 is a potent eukaryotic initiation factor 4A (eIF4A) inhibitor. It inhibits NIH 3T3 cells (IC50: 10 nM). CMLD012073 inhibits eukaryotic translation initiation by modifying the behavior of the RNA helicase (eIF4A).

CMLD012612 is a potent eukaryotic initiation factor 4A (eIF4A) inhibitor. It inhibits cell translation and is cytotoxic to NIH 3T3 cells (IC50: 2 nM).

CMLD-2 is an inhibitor of HuR-ARE interaction (Ki: 350 nM) that competitively binds HuR protein and disrupts its interaction with adenine element-rich (ARE) mRNA targets.CMLD-2 induces apoptosis and exhibits antitumor effects through MAD2 downregulation. CMLD-2 (1-75 μM ; 24-72 h) had an inhibitory effect on the viability of thyroid cancer cells.CMLD-2 (20-30 μM ; 24-48 h) activated caspases and induced apoptosis in H1299 and A549 cells.CMLD-2 (30 μM ; 24-48 h) induced G1 cell cycle arrest in H1299 and A549 cells and mitochondrial perturbation. CMLD-2 (30 μM ; 24-48 h) reduced the expression of HuR and HuR-regulated mRNAs and proteins in H1299 cells.CMLD-2 (35 μM ; 72 h) decreased the directional migration ability of SW1736, 8505C, BCPAP and K1 cells.CMLD-2 induced the migration of SW1736, 8505C, BCPAP and K1 cells with a strong decrease in MAD2 mRNA levels.

AN-019 (NRC-019) is a Bcr-Abl kinase inhibitor with antitumor activity for the study of chronic myelogenous leukemia (CML) and breast cancer.

SKLB 1028 (Ruserontinib) is a new type of oral multikinase inhibitor of EGFR, FLT3, and Abl. SKLB 1028 shows excellent activity in FLT3-driven AML models and considerable potency in CML models containing Abl mutants.

Isoprenaline hydrochloride (NCI-c55630) is a potent beta-adrenergic agonist with the peripheral vasodilator, bronchodilator, and cardiac stimulating properties.

Nilotinib (AMN107) is a Bcr-Abl tyrosine kinase inhibitor with oral activity. Nilotinib has antitumor activity and may be used for the treatment of Imatinib-resistant chronic myelogenous leukemia (CML).

Pivanex (Pivalyloxymethyl butyrate) is an orally active HDAC inhibitor and an antimetastatic and antiangiogenic agent. Pivanex downregulates the Bcr-Abl protein and enhances apoptosis.

1. trans-Cinnamaldehyde (Phenylacrolein) exhibits excellent anti-inflammatory activities and antidepressant-like effects in stressed mid-aged rats as a COX-2 inhibitor. 2. Cinnamic aldehyde induces apoptosis of CML cells in vitro, down-regulation of the expression and function of BCR-ABL may be one of its most important anti-leukemia mechanisms. 3. Cinnamic aldehyde and cinnamic acid are cardioprotective in a rat model of ischemic myocardial injury, the mechanism is related to anti-oxidative and anti-inflammatory properties.

iHCK-37 (ASN05260065) is a selective Hck inhibitor with antitumor activity, blocking HIV-1 viral replication. iHCK-37 reduces PI3K AKT and MAPK ERK pathway activation after erythropoietin induction in high Hck-expressing cells, useful in chronic myelogenous leukemia (CML) research.

Icaritin (Anhydroicaritin) has hormone regulation activity and cardiovascular function improvement activity. Icaritin has anticancer activity, can induce S phase arrest and apoptosis, inhibit ENKL cell proliferation. Icaritin has anti-multiple myeloma activity, mainly mediated by inhibiting IL-6 JAK2 STAT3 signaling. Icaritin at low concentration (4 or 8 μMol L) can promote rat chondrocyte proliferation and inhibit cell apoptosis, while the effect of Icaritin on rat chondrocyte at high concentration was reversed.

1. Oroxylin A (Baicalein 6-methyl ether) has various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion. 2. Oroxylin A possesses abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP LIP CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS. 3. Oroxylin A inhibits UCP2s triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells; uncoupling protein 2 plays a key role in mitochondrial apoptotic pathway. 4. Oroxylin A inhibits N1ICD translocating to the nucleus and binding to epithelial-mesenchymal transition-related transcription factor Snail, thus suppressing the invasion and migration of MCF-7 cells. 5. Oroxylin A improves the sensitivity of K562 ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K Akt NF-κB pathway, and probably served as a most promising agent for CML treatment.

GNF-5 is a specific non-ATP competitive inhibitor of Bcr-Abl (IC50: 0.22±0.1 uM, Wild-type Abl). It is an analog of GNF-2 with improved pharmacokinetic properties.

Adaphostin (NSC-680410) is a p210Bcr Abl tyrosine kinase inhibitor with IC50 of 14 μM.

CT-721 is a potent, time-dependent Bcr-Abl kinase inhibitor with an IC50 of 21.3 nM against wild-type Bcr-Abl kinase, exhibiting anti-chronic myeloid leukemia (CML) activity.

BCR-ABL-IN-10 (compound B4) is a covalent BCR-ABL inhibitor featuring an arylvinylsulfonate (AVS) moiety, demonstrating an IC50 of 43.1 nM against ABL kinase. It forms a covalent and stable adduct with ABL kinase, enabling the sustained inhibition of intrinsic BCR-ABL activity. This compound is utilized in the study of chronic myeloid leukemia (CML).

S1g-10 is an Hsp70 Bim inhibitor that exhibits significant antitumor activity, particularly in chronic myeloid leukemia (CML) cells. It inhibits the protein-protein interaction between Hsp70 and Bim, blocking cancer cell survival signals and inducing apoptosis. S1g-10 is an optimized derivative of S1g-2, with a 10-fold increase in anticancer potency.

Purinostat is a selective inhibitor of HDACI IIb with potential anti-leukemic properties. Its mesylate form, Purinostat mesylate, is effective at inhibiting the survival of Ph+ leukemic cells and CD34+ leukemic cells derived from CML patients. Purinostat mesylate targets HDACI IIb, impacting several crucial factors for leukemia stem cell (LSC) survival, such as c-Myc, β-Catenin, E2f, Ezh2, Alox5, and mTOR. Additionally, Purinostat mesylate enhances glutamate metabolism in LSCs by increasing GLS1.

MMP-2Inhibitor-4 (Compound 5g) is an MMP-2 inhibitor with an IC50 of 152.62 nM. It effectively reduces MMP-2 levels in K562 cell lines by stably binding to the active site of MMP-2 and exhibits strong anti-angiogenic effects in ACHN cell lines. MMP-2Inhibitor-4 shows potential for research in chronic myelogenous leukemia (CML).