| DC75073 |
BGP-15 HCl |
BGP-15 is a novel poly(ADP-ribose) polymerase inhibitor - protects against nephrotoxicity of cisplatin without compromising its antitumor activity. BGP-15 also inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury. Moreover, BGP-15 was found to prevent imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases. |
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| DC75074 |
Allitinib tosylate |
Allitinib, also known as AST1306 and ALS 1306, is a potent, selective, irreversible ErbB2 and EGFR inhibitor. AST-1306 inhibits the enzymatic activities of wild-type epidermal growth factor receptor (EGFR) and ErbB2 as well as EGFR resistant mutant in both cell-free and cell-based systems. AST1306 was found to function as an irreversible inhibitor, most likely through covalent interaction with Cys797 and Cys805 in the catalytic domains of EGFR and ErbB2, respectively. In vivo, AST1306 potently suppressed tumor growth in ErbB2-overexpressing adenocarcinoma xenograft and FVB-2/N(neu) transgenic breast cancer mouse models, but weakly inhibited the growth of EGFR-overexpressing tumor xenografts. |
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| DC75075 |
BAY 61-3606 |
BAY 61-3606 is a potent (Ki = 7.5 nM) and selective inhibitor of Syk kinase. BAY 61-3606 inhibited not only degranulation (IC50 values between 5 and 46 nM) but also lipid mediator and cytokine synthesis in mast cells. BAY 61-3606 was highly efficacious in basophils obtained from healthy human subjects (IC50 = 10 nM) and seems to be at least as potent in basophils obtained from atopic (high serum IgE) subjects (IC50 = 8.1 nM). B cell receptor activation and receptors for Fc portion of IgG signaling in eosinophils and monocytes were also potently suppressed by BAY 61-3606. |
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| DC75076 |
UAMC-3203 HCl |
UAMC-3203 is a Ferroptosis Inhibitor wtih IC50 = 12 nM. UAMC-3203 showed an improved protection compared to Fer-1 against multiorgan injury in mice. No toxicity was observed in mice after daily injection of UAMC-3203 for 4 weeks. UAMC-3203 inserts rapidly in a phospholipid bilayer in silico, which aligns with the current understanding of the mechanism of action of these compounds. In conclusion, these analogues have superior properties compared to Fer-1, show in vivo efficacy, and represent novel lead compounds with therapeutic potential in relevant ferroptosis-driven disease models. |
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| DC75077 |
BSJ-03-123 HCl |
BSJ-03-123 is a potent, CDK6-selective small-molecule degrader (PROTAC). Pharmacologic CDK6 degradation targets a selective dependency of acute myeloid leukemia cells, and transcriptomics and phosphoproteomics profiling of acute degradation of CDK6 enabled dynamic mapping of its immediate role in coordinating signaling and transcription. |
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| DC75078 |
FLX925 (AMG-925) |
FLX925, also known as AMG-925, is a potent and selective type 1 inhibitor of FLT3 that retains its cellular potency against clinically relevant secondary resistance mutations in FLT3 occurring with quizartinib or sorafenib treatment (FLX925 IC50: MOLM13ITD, 15 nM; MOLM13ITD/D835, 28 nM; MV4-11ITD, 16 nM; MV4-11ITD/D835, 19 nM; MV4-11ITD/N841, 16 nM; MV4-11ITD/F691, 73 nM). |
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| DC75079 |
Elacestrant HCl |
Elacestrant, also known as RAD1901, is an orally available, selective estrogen receptor degrader (SERD) and selective estrogen receptor modulator (SERM), with potential antineoplastic and estrogen-like activities. Upon oral administration of higher doses of RAD1901, this agent acts as a SERD, which binds to the estrogen receptor (ER) and induces a conformational change that results in the degradation of the receptor. This may inhibit the growth and survival of ER-expressing cancer cells. At lower doses of this agent, RAD1901 acts as a SERM and has estrogen-like effects in certain tissues, which can both reduce hot flashes and protect against bone loss. In addition, RAD1901 is able to cross the blood-brain barrier (BBB). |
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| DC75080 |
Tamatinib free base |
Tamatinib, also known as R406, is a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling (EC(50) for degranulation = 56-64 nM). The primary target for R406 is the spleen tyrosine kinase (Syk). R406 inhibited phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 bound to the ATP binding pocket of Syk and inhibited its kinase activity as an ATP-competitive inhibitor (K(i) = 30 nM). |
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| DC75081 |
Quizartinib HCl |
Quizartinib, also known as AC220 and AC010220, is a highly potent FMS-like receptor tyrosine kinase-3 (FLT3) inhibitor. Quizartinib HCl inhibits FLT3 activity and displays antitumor properties in a mouse MV4-11 tumor xenograft model. |
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| DC75082 |
Bimiralisib free base |
Bimiralisib, also known as PQR309, is an orally bioavailable pan inhibitor of phosphoinositide-3-kinases (PI3K) and inhibitor of the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. PI3K/mTOR kinase inhibitor PQR309 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy. |
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| DC75083 |
Neratinib |
Neratinib, also known as HKI-272 or PB272, is an orally available, irreversible inhibitor of the HER-2 receptor tyrosine kinase with potential antineoplastic activity. Neratinib binds to the HER-2 receptor irreversibly, thereby reducing autophosphorylation in cells, apparently by targeting a cysteine residue in the ATP-binding pocket of the receptor. |
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| DC75084 |
Xaliproden HCl |
Xaliproden, also known as SR57746, is a drug which acts as a 5HT1A agonist. It has neurotrophic and neuroprotective effects in vitro, and has been proposed for use in the treatment of several neurodegenerative conditions including amyotrophic lateral sclerosis and Alzheimer's disease. The SR57746A activates PI3-K/AKT- and ERK-signaling in IECs. Depending on ERK- and AKT activation, SR57746A potently prevents apoptosis of IECs without inducing proliferation or migration in these cells. Moreover, SR57746A prevented apoptosis in EGCs in vitro. Topical SR57746A treatment significantly reduced mucosal injury in 2 experimental murine colitis models and was as effective as intraperitoneal infliximab treatment. |
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| DC75085 |
Ensartinib free base |
Ensartinib, also known as X-396, is an orally available small molecule inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with potential antineoplastic activity. Upon oral administration, X-396 binds to and inhibits ALK kinase, ALK fusion proteins and ALK point mutation variants. Inhibition of ALK leads to the disruption of ALK-mediated signaling and eventually inhibits tumor cell growth in ALK-expressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. |
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| DC75086 |
Defactinib free base |
Defactinib, also known as VS-6063 and PF-04554878, is an orally bioavailable, small-molecule focal adhesion kinase (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. FAK inhibitor PF-04554878 inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including ERK, JNK/MAPK and PI3K/Akt, thus inhibiting tumor cell migration, proliferation and survival. |
|
| DC75087 |
Peficitinib free base |
Peficitinib, also known as ASP015K and JNJ-54781532, is a novel potent JAK inhibitor, which demonstrated potent efficacy in adjuvant-induced arthritis model in rats. ASP015K inhibited JAK1, JAK2, JAK3 and TYK2 enzyme activities with IC50 values of 3.9, 5.0, 0.71 and 4.8 nM, respectively. ASP015K inhibited the IL-2-induced proliferation of human T cells with an IC50value of 18 nM. Moreover, ASP015K was 14-fold more potent against JAK1/3 than JAK2/2 on the basis of EPO-induced proliferation of human leukemia cells. |
|
| DC75088 |
PD-153035 free base |
PD153035 is a ATP-competitive EGFR inhibitor with an IC50 and Ki of 25 and 6 pM. PD153035 effectively blocks the enhancement of mitogenesis, induction of early gene expression, and oncogenic transformation that occur in response to EGF receptor stimulation. With human fibroblasts and epidermoid carcinoma cells, PD153035 at nanomolar concentrations rapidly inhibits EGFR autophosphorylation. With breast and ovarian cancer cells, PD153035 not only blocks cell growth via inhibition of EGFR, but also upregulates the expression of the tumor suppressor retinoic acid receptor-beta 2 (RAR-beta2). |
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| DC75089 |
Palifosfamide-Tris |
Palifosfamide, also known as ZIO201, is a synthetic mustard compound with potential antineoplastic activity. An active metabolite of ifosfamide covalently linked to the amino acid lysine for stability, palifosfamide irreversibly alkylates and cross-links DNA through GC base pairs, resulting in irreparable 7-atom inter-strand cross-links; inhibition of DNA replication and cell death follow. Unlike ifosfamide, this agent is not metabolized to acrolein or chloroacetaldehyde, metabolites associated with bladder and CNS toxicities. In addition, because palifosfamide does not require activation by aldehyde dehydrogenase, it may overcome the tumor resistance seen with ifosfamide. |
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| DC75090 |
AV-412 Tosylate |
AV-412, also known as MP-412, is a second-generation, orally bioavailable dual kinase inhibitor with potential antineoplastic activity. EGFR/HER2 inhibitor AV-412 binds to and inhibits the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2), which may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors. This agent may be active against EGFR/HER2-expressing tumor cells that are resistant to first-generation kinase inhibitors. EGFR and HER2 are receptor tyrosine kinases that play major roles in tumor cell proliferation and tumor vascularization. |
|
| DC75091 |
Pacritinib (SB1518) |
Pacritinib, also known as SB1518, is an orally bioavailable inhibitor of Janus kinase 2 (JAK2) and the JAK2 mutant JAK2V617F with potential antineoplastic activity. Pacritinib competes with JAK2 for ATP binding, which may result in inhibition of JAK2 activation, inhibition of the JAK-STAT signaling pathway, and so caspase-dependent apoptosis. JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorders; the JAK2V617F gain-of-function mutation involves a valine-to-phenylalanine modification at position 617. The JAK-STAT signaling pathway is a major mediator of cytokine activity. |
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| DC75092 |
LXH254 free base |
Naporafenib, also known as LXH254, is an orally available inhibitor of all members of the serine/threonine protein kinase Raf family, with potential antineoplastic activity. Upon administration, pan-RAF inhibitor LXH254 binds to Raf proteins and inhibits Raf-mediated signal transduction pathways. This inhibits proliferation of Raf-overexpressing tumor cells. Raf protein kinases are critical enzymes in the Ras/Raf/MEK/ERK signaling pathway and are upregulated in a variety of cancer cell types. |
|
| DC75093 |
Cediranib free base |
Cediranib, also known as AZD-2171, is a potent and selective VEGF inhibitor with antineoplastic activities. Competing with adenosine triphosphate, cediranib binds to and inhibits all three vascular endothelial growth factor receptor (VEGF-1,-2,-3) tyrosine kinases, thereby blocking VEGF-signaling, angiogenesis, and tumor cell growth. |
|
| DC75094 |
Rucaparib Camsylate |
Rucaparib camsylate is a potent, orally available inhibitor of poly ADP-ribose polymerase (PARP) 1 and 2. |
|
| DC75095 |
Molidustat |
Molidustat, also known as BAY 85-3934, is a novel inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) which stimulates erythropoietin (EPO) production and the formation of red blood cells. Phase I data have shown that inhibition of HIF-PH by Molidustat results in an increase in endogenous production of EPO. Molidustat is currently clinical trials at Bayer for the treatment of patients suffering from renal anemia due to chronic kidney disease. |
|
| DC75096 |
GDC-0575 freebase |
GDC-0575, also known as ARRY-575 and RG7741, is a potent and selective inhibitor of cell cycle checkpoint kinase 1 (Chk1) with an IC50 of 1.2 nM. Chk1 inhibitor GDC-0575 specifically binds to and inhibits Chk1; this may result in tumor cells bypassing Chk1-dependent cell cycle arrest in the S and G2/M phases, which permits the cells to undergo DNA repair prior to entry into mitosis. |
|
| DC75097 |
Mocetinostat (MGCD-0103) |
Mocetinostat, also known as MGCD-0103, is a rationally designed, orally available, Class 1-selective, small molecule, 2-aminobenzamide HDAC inhibitor with potential antineoplastic activity. Mocetinostat binds to and inhibits Class 1 isoforms of HDAC, specifically HDAC 1, 2 and 3, which may result in epigenetic changes in tumor cells and so tumor cell death; although the exact mechanism has yet to be defined, tumor cell death may occur through the induction of apoptosis, differentiation, cell cycle arrest, inhibition of DNA repair, upregulation of tumor suppressors, down regulation of growth factors, oxidative stress, and autophagy, among others. |
|
| DC75098 |
Memantine free base |
Memantine is an amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent and has may be used to treat moderate to severe Alzheimer's disease. It acts on the glutamatergic system by blocking NMDA receptors. |
|
| DC75099 |
RG7834 |
RG7834, also known as RO7020322, is a novel oral HBV viral gene expression inhibitor that blocks viral antigen and virion production. RG7834 is highly selective for HBV, and has a unique antiviral profile that is clearly differentiated from nucleos(t)ide analogues. |
|
| DC75100 |
Alifedrine HCl |
Alifedrine, also known as D13625, is a positive inotropic agent. Alifedrine moderately reduces the severity of ischaemia and reperfusion-induced ventricular arrhythmias. Alifedrine has an unusual and useful spectrum of pharmacological activity in that it combines antiarrhythmic activity with an ability to improve cardiac function. Alifedrine in the tested model markedly improved left ventricular function by balanced stimulation of the myocardium and reduction of pre- and afterload. |
|
| DC75101 |
Ixazomib (MLN-2238) |
Ixazomib, also known as MLN-2238, is a potent proteasome inhibitor (PI) with potential antineoplastic activity. MNL-2238 is also .the biologically active form of MLN9708. MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMyc(Cα)/Bcl-X(L) GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model. |
|
| DC75102 |
Alentemol HBr |
Alentemol, also known as U-66444B and alentamol, is a selective dopamine autoreceptor agonist described as an antipsychotic. Chromosomal breakage following treatment of CHO-K1 cells in vitro with U-68,553B is due to induction of undercondensation of heterochromatin. |
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