chemotherapy-induced

Fosaprepitant dimeglumine (MK-0517) is the dimeglumine salt form of fosaprepitant, a water-soluble, N-phosphorylated prodrug of aprepitant with antiemetic activity. Upon intravenous administration and rapid conversion to aprepitant, this agent selectively binds to human substance P/neurokinin 1 (NK1) receptors in the central nervous system (CNS), inhibiting receptor binding of endogenous substance P and preventing substance P-induced emesis.

ACY-1083 is a small molecule inhibitor, a highly selective HDAC6 inhibitor (IC50=3 nM), with 260-fold higher selectivity over other classes of HDAC isoforms. It is brain-penetrant and used for research on chemotherapy-induced peripheral neuropathy.

Phenothiazine (ENT 38) is a class of agents exhibiting antiemetic, antipsychotic, antihistaminic, and anticholinergic activities. Phenothiazines antagonize the dopamine D2-receptor in the chemoreceptor trigger zone (CTZ) of the brain, potentially preventing chemotherapy-induced emesis.

Palonosetron hydrochloride (RS 25259) is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting.

Anethole trithione (Anetholtrithion) is a bile secretion-stimulating drug that restores salivation and relieves the discomfort of dry mouth in chemotherapy-induced xerostomia.

Acetyl-L-carnitine hydrochloride (Acetyl L-carnitine hydrochloride) is a nutritional supplement composed of the hydrochloride salt form of the acetylated form of the endogenously produced L-carnitine, with potential neuroprotective, cognitive-enhancing, anti-depressive and immunomodulating activities. It may also relieve peripheral neuropathy induced by chemotherapy, diabetes or other diseases. In addition, acetyl-L-carnitine may modulate the immune response by increasing T-lymphocytes maturation and may downregulate pro-inflammatory cytokines in response to viruses, such as SARS-CoV-2. It may also disrupt the ACE2 signaling pathway and inhibit the production of reactive oxygen species (ROS).

KLS-13019 is a highly effective and orally active GPR55 receptor antagonist, a cannabidiol (CBD)-derived neuroprotective agent that can reverse chemotherapy-induced peripheral neuropathy (CIPN) and is suitable for studying hepatic encephalopathy (HE).

EX-A5758 is a novel putative small molecule nNOS-NOS1AP inhibitor, suppressing inflammatory nociception and chemotherapy-induced neuropathic pain and synergizes with paclitaxel to reduce tumor cell viability.

Trilaciclib is a short-acting, orally effective CDK4/6 inhibitor with IC₅₀ values of 1 nM and 4 nM respectively. It transiently and reversibly induces G1 cell cycle arrest, mitigates chemotherapy-induced myelosuppression, and enhances antitumour immunity, making it applicable across multiple cancers.

(R,R)-Palonosetron Hydrochloride, the active enantiomer of Palonosetron, is a selective 5-HT3 receptor antagonist used primarily for the prevention of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV).

PF-477736, also known as PF-00477736, is a potent CHK1 inhibitor with potential to enhance chemotherapy. This compound inhibits CHK1, an ATP-dependent serine/threonine kinase that is a crucial component of the S/G2 checkpoint system for DNA replication monitoring. By bypassing the final checkpoint defenses against DNA damage-induced lethal effects, PF-477736 may improve the antitumor efficacy of various chemotherapeutic agents in tumor cells with inherent checkpoint deficiencies.

Casopitant (GW679769) is an orally active neurokinin-1 (NK1) receptor antagonist, researched for its potential use in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV).

Mangafodipir is a hepatocyte-specific contrast agent and an effective inhibitor of conditions caused by CIPN (chemotherapy-induced peripheral neuropathy) and other oxidative stress pathways. It does not negatively impact the tumor-killing efficacy of chemotherapy.

TrkA Inhibitor (Compound 18) acts as a CDK2 inhibitor with an IC50 of 0.69 μM, demonstrating greater potency compared to CDK1 inhibition. It is applicable in studies related to chemotherapy-induced hair loss.

MU876 (Compound 32) is an MUS81 inhibitor with an IC50 of 0.5 μM. It effectively inhibits MUS81-dependent homologous recombination (HR) and break-induced replication (BIR) pathways. MU876 enhances the sensitivity of cancer cells to DNA-damaging agents like Cisplatin by impairing their ability to repair DNA damage. This compound is applicable in cancer chemotherapy research.

Axl-IN-21 is an orally bioavailable selective AXL inhibitor with a Kd of 2.7 nM and an IC50 of 4.0 nM. It demonstrates strong inhibitory activity against various cancer-related kinases while maintaining kinase selectivity, including Mer (Kd = 1.4 nM), DDR1 (IC50 = 22.2 nM), HIPK4 (Kd = 11.0 nM), and LOK (Kd = 10 nM). By blocking the AXL/STAT3/ABCG1 signaling pathway induced by GAS6 from tumor-associated fibroblasts, Axl-IN-21 can overcome tumor microenvironment-driven resistance, restore chemotherapy sensitivity, and inhibit drug efflux. In MDA-MB-231 cells, it inhibits TGF-β1-induced epithelial-mesenchymal transition, cell migration, and invasion. Axl-IN-21 exhibits no significant toxicity to non-cancer cells and is relevant for research in triple-negative breast cancer and gastric cancer.

Carba1 is a bifunctional carbazole derivative that activates nicotinamide phosphoribosyltransferase (NAMPT) and enhances the biosynthesis of NAD. It binds to the colchicine site on tubulin, potentially boosting the antitumor effects of various chemotherapeutics such as Paclitaxel. Carba1 has neuroprotective properties and regulates cellular energy metabolism. It is applicable in research on cancer and chemotherapy-induced peripheral neuropathy (CIPN).

Dolasetron Mesylate (MDL-73147EF) is a 5-HT3 receptor antagonist used in research focused on treating chemotherapy-induced nausea and vomiting.

Palonosetron, a 5-HT3 antagonist with Ki of 0.17 nM, is used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV).

Dolasetron Mesylate hydrate (Dalasetron Mesylate Hydrate) , a selective serotonin receptor antagonist, competitively blocks the action of serotonin at 5HT3 receptors, resulting in suppression of chemotherapy- and radiotherapy-induced nausea and vomiting.

Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg/kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg/kg twice daily.3 Alaproclate (40 mg/kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988). Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg/kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg/kg twice daily.3 Alaproclate (40 mg/kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4 References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988).

Rolapitant (SCH619734) Hydrochloride is the hydrochloride salt form of rolapitant, an orally bioavailable, centrally-acting, selective, neurokinin 1 receptor (NK1-receptor) antagonist with potential antiemetic activity. Upon oral administration, rolapitant competitively binds to and blocks the activity of the NK1-receptor in the central nervous system, thereby inhibiting the binding of the endogenous ligand, substance P (SP). This may prevent both SP-induced emesis and chemotherapy-induced nausea and vomiting (CINV). The interaction of SP with the NK1-receptor plays a key role in the induction of nausea and vomiting caused by emetogenic cancer chemotherapy. Compared to other NK1-receptor antagonists, rolapitant has both a more rapid onset of action and a much longer half-life.

(±)14(15)-EpETE, an eicosatetraenoic acid derivative containing an epoxy group, is an intestinal microbial lipid metabolite that attenuates cisplatin chemotherapy-induced nausea and vomiting in rats by inhibiting Substance P release through targeting GCG/PKA signaling and is commonly used to study inflammation and metabolism.

Fabesetron (FK1052) is an orally active compound that acts as a dual antagonist of 5-HT3 and 5-HT4 receptors, demonstrating efficacy in managing emesis induced by cancer chemotherapy and showing potential for addressing both acute and delayed symptoms.