anti-myeloma

PTC-209 hydrobromide (PTC-209 HBr) is the hydrobromide salt of PTC-209, which is a potent and selective BMI-1 inhibitor with IC50 of 0.5 μM, and results in irreversible reduction of cancer-initiating cells (CICs).

Magrolimab (Hu5F9-G4) is a humanized anti-CD47 IgG4 monoclonal antibody that exhibits antitumor activity by blocking CD47 and binding primarily to the N-terminal pyroglutamate of CD47. It can be used in combination with other compounds for the treatment of recurrent myeloma.

Mezigdomide (CC-92480) is a potent, novel, selective and active cereblon E3 ubiquitin ligase modulator (CELMoD) that acts as a molecular glue. Mezigdomide has anti-myeloma activity. [1]

(S)-Thalidomide ((S)-(-)-Thalidomide) is the S-isomer of Thalidomide with immunomodulatory, anti-inflammatory, anticancer, anti-angiogenic, and pro-apoptotic activities, used in studying leprosy erythema nodosum and myeloma.

DCZ0415 induces antimyeloma activity in vitro, in vivo and in primary cells of drug-resistant myeloma patients. DCZ0415 is a potent TRIP13 inhibitor that can impair the repair of non-homologous end junctions and inhibit NF-κB activity.

PTC-209 is a potent and selective BMI-1 inhibitor.

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.

CCF642 (AC1LYELL) is a novel PDI-inhibiting compound with antimyeloma activity.

E64FC26 is a potent protein disulfide isomerase (PDI) family pan-inhibitor with antitumor activity, inhibits PDIA1, PDIA3, PDIA4, TXNDC5 and PDIA6, and can be used in the study of multiple myeloma and pancreatic cancer.

(R)-BAY1238097 represents the R-isomer of BAY1238097, which exhibits relatively lower activity compared to its counterpart. BAY1238097 is a highly potent and selective inhibitor targeting the binding of BET proteins to histones, demonstrating significant anti-proliferative effects in various acute myeloid leukemia (AML) and multiple myeloma (MM) models. The high activity is achieved through the down-regulation of c-Myc levels and the subsequent modulation of its downstream transcriptome.

Dolastatin 15, a depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the anti-tubulin agent Dolastatin 10. Dolastatin 15 can be used as an ADC cytotoxin and it induces cell cycle arrest and apoptosis in m

SLM6, an inhibitor of cyclin-dependent kinase-9 (CDK9), exhibits potent anti-multiple myeloma activity.

Elotuzumab(HuLuc 63) is a monoclonal antibody that targets the SLAMF7 receptor.Elotuzumab is a compound that directly activates NK cells and induces antibody-dependent cytotoxicity, and can be used in combination with lenalidomide and dexamethasone (Ld) to treat multiple myeloma.

ACY-241, also known as Citarinostat (ACY241), is a potent, selective and orally available histone deacetylase (HDAC) inhibitor, with potential antineoplastic activity. Upon oral administration, ACY-241 inhibits the activity of HDACs; this results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This leads to the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes, which inhibit tumor cell division and induce tumor cell apoptosis.

LSD1 HDAC6-IN-1 is an orally active dual inhibitor targeting lysine specific demethylase 1 (LSD1) and histone deacetylase 6 (HDAC6), demonstrating promising anti-tumor activity, particularly valuable for multiple myeloma (MM) research [1].

KRAS inhibitor-10 (WO2021005165 A1, compound 11) is a potent and selective inhibitor of RAS proteins, with a specific focus on KRAS proteins. This orally active anti-cancer agent demonstrates strong efficacy in cancer research, specifically in pancreatic cancer, breast cancer, multiple myeloma, leukemia, and lung cancer. KRAS inhibitor-10 is classified as a tetrahydroisoquinoline compound. Its inhibitory properties provide valuable insights and potential therapeutic applications in the field of oncology [1].

Antitumor agent-70 (compound 8b) is a highly potent multi-targeted kinase inhibitor, particularly targeting c-Kit. It demonstrates remarkable anti-tumor activity and induces cell apoptosis, with strong inhibition of multiple myeloma at an IC50 value of 0.12 μM. Therefore, Antitumor agent-70 holds great potential as an effective therapy for combating cancer, especially in cases involving c-Kit. [1]

HDAC6-IN-10 is a potent and specific HDAC6 inhibitor, exhibiting an IC50 value of 0.73 nM. It demonstrates remarkable selectivity towards HDAC6, with a selectivity range of 144 to 10,941-fold over other HDAC isoforms. Furthermore, HDAC6-IN-10 exhibits notable anti-proliferative effects on multiple myeloma cells [1].

HGGPPS-IN-1 is an analogue of C-2-substituted thienopyrimidine-based bisphosphonates (C2-ThP-BPs). HGGPPS-IN-1 has an effective inhibitory effect on human geranyl geranyl pyrophosphate synthase (hGGPPS). HGGPPS-IN-1 can selectively induce apoptosis of multiple myeloma (MM) cells. HGGPPS-IN-1 showed anti-myeloma activity in vivo.

TAS-117 hydrochloride is a selective, potent, orally active allosteric Akt inhibitor, acting on Akt1 (IC50: 4.8 nM), Akt2 (IC50: 1.6 nM) and Akt3 (IC50: 44 nM). TAS-117 hydrochloride stimulates anti-myeloma activity, enhances lethal endoplasmic reticulum stress induced by proteasome inhibition, and can induce apoptosis and autophagy.

hGGPPS-IN-2 is an analogue of C-2 substituted thienopyrimidinyl bisphosphonates (C2-ThP-BPs) and is a potent inhibitor of human geranylgeranyl pyrophosphate synthase (hGGPPS). hGGPPS-IN-2 targets multiple myeloma (MM) cells, induces selective apoptosis, and shows anti-myeloma effects in vivo. It has shown anti-myeloma effects in vivo.

Dexamethasone sodium succinate is the acetate salt form of dexamethasone, which is a synthetic glucocorticoid; it combines high anti-inflammatory effects with low mineralocorticoid activity. At high doses (e.g. 40 mg), it reduces the immune response. Dexamethasone acetate (NEOFORDEX®) is indicated in adults for the treatment of symptomatic multiple myeloma in combination with other medicinal products. Dexamethasone has been shown to induce multiple myeloma cell death (apoptosis) via a down-regulation of nuclear factor-κB activity and an activation of caspase-9 through second mitochondria-derived activator of caspase (Smac; an apoptosis promoting factor) release. Prolonged exposure was required to achieve maximum levels of apoptotic markers along with increased caspase-3 activation and DNA fragmentation. Dexamethasone also down-regulated anti apoptotic genes and increased IκB-alpha protein levels. Dexamethasone apoptotic activity is enhanced by the combination with thalidomide......

AMP423 is a naphthyl derivative of 2-cyanoaziridine-1-carboxamide with structural similarity to the pro-oxidant anti-tumor agent imexon. AMP423 was active in SCID mice bearing 8226 S myeloma and SU-DHL-6 B-cell lymphoma tumors, with a median tumor growth delay (T-C) of 21 days (P = 0.0002) and 5 days (P = 0.004), respectively, and a median tumor growth inhibition (T C) of 33.3% (P = 0.03) and 82% (P = 0.01), respectively. In non-tumor-bearing mice, AMP423 was not myelosuppressive.

BT-GSI, a γ-secretase inhibitor (GSI) with bone-targeting capabilities, effectively inhibits Notch signaling. Exhibiting dual action, it possesses both anti-myeloma and anti-resorptive properties, making it a promising candidate for research into multiple myeloma and related bone diseases. Additionally, BT-GSI demonstrates potential in inhibiting tumor growth and the progression of osteolytic disease.