| DC75125 |
Crenigacestat |
Crenigacestat, also known as LY3039478, is a orally bioavailable, novel small molecule Notch inhibitor with an IC50 of ~1nM in most of the tumor cell lines tested. LY3039478 potently inhibits mutant Notch receptor activity. In a xenograft tumor model, LY3039478 inhibited N1ICD cleavage and expression of Notch-regulated genes in the tumor microenvironment. LY3039478 is being investigated in Phase I. |
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| DC75126 |
Ixazomib citrate |
Ixazomib citrate, also known as MLN9708, is a prodrug of Ixazomib (MMLN-2238). MLN9708 is an orally bioavailable second generation proteasome inhibitor (PI) with potential antineoplastic activity. MLN9708, after hydrolyzing to pharmacologically active MLN2238 (ixazomib), is a next-generation proteasome inhibitor with demonstrated preclinical and clinical antimyeloma activity. MLN9708, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. |
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| DC75127 |
Asciminib HCl |
Asciminib, also known as ABL001, is a potent allosteric inhibitor of BCR-ABL. ABL001 prevents emergence of resistant disease when administered in combination with nilotinib in an in vivo murine model of chronic myeloid leukemia. Cell proliferation studies demonstrate that ABL001 selectively inhibited the growth of CML and Ph+ ALL cells with potencies ranging from 1-10nM range. ABL001 was tested for activity against clinically observed mutations and found to be active in the low nM range. In the KCL-22 mouse xenograft model, ABL001 displayed potent anti-tumor activity with complete tumor regression observed and a clear dose-dependent correlation with pSTAT5 inhibition. |
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| DC75128 |
Glycovir |
Glycovir, also known as SC-49483, is an anti-HIV prodrug. Glycovir is an alpha-glucosidase-1 inhibitor, and a candidate anti-HIV agent targeted against viral glycoprotein processing in host cell endoplasmic reticulum. |
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| DC75129 |
Bemitradine |
Bemitradine is a diuretic antihypertensive agent. |
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| DC75130 |
Merestinib (LY2801653) |
Merestinib, also known as LY2801653, is an orally available, small molecule inhibitor of the proto-oncogene c-Met (mesenchymal-epithelial transition, also known as hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor LY2801653 selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. This agent has potent anti-tumor efficacy in mono- and combination therapy in a broad range of cancers. |
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| DC75131 |
Itacitinib |
Itacitinib, also known as INCB39110 or INCB039110, is a potent JAK1 tyrosine kinase inhibitor, which is currently in Phase II trials for the treatment of rheumatoid arthritis, myelofibrosis, rheumatoid arthritis and plaque psoriasis. INCB039110 produced significant improvements in sPGA, demonstrating proof of concept in chronic plaque psoriasis. |
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| DC75132 |
BIIB021 |
BIIB021, also known as CNF2024, is an orally active, purine-scaffold, small-molecule inhibitor of heat shock protein 90 (HSP90) with potential antineoplastic activity. HSP90 inhibitor CNF2024 specifically blocks active HSP90, inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival; this may result in the inhibition of cellular proliferation in susceptible tumor cell populations. |
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| DC75133 |
Prexasertib free base |
Prexasertib, also know LY2606368, is a small molecule checkpoint kinase inhibitor that causes DNA double-strand breaks, which results in apoptosis. Prexasertib is mainly active against CHEK1, with minor activity against CHEK2. Preclinical studies have shown that prexasertib induces DNA damage and tumor cell apoptosis in monotherapy. Prexasertib may also potentiate the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapeutic agents. |
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| DC75134 |
Meldonium dihydrate |
Meldonium is a structural analog of gamma-butyrobetaine used to treat coronary artery disease |
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| DC75135 |
Dactolisib |
Dactolisib, also known as BEZ235, is an orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor BEZ235 specifically inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability; apoptotic cell death may ensue. Bax is a member of the proapoptotic Bcl2 family of proteins. |
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| DC75136 |
Olmutinib free base |
Olmutinib, also known as HM61713 and BI-1482694, is a potent small molecule inhibitor of Bruton's tyrosine kinase (BTK). BTK is a member of the Tec family of non-receptor protein tyrosine kinases. BTK is mostly expressed in hematopoietic cells such as B cells, mast cells and macrophages. BTK plays key roles in multiple cell signaling pathways including B-Cell Receptor (BCR) and Fc receptor (FcR) signaling cascades and is an essential mediator not only in B-cell dependent but also in myeloid cell dependent inflammatory arthritis. HM71224 has been selected as a novel therapeutic agent for the treatment of autoimmune diseases such as RA. |
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| DC75137 |
Lesinurad free acid |
Lesinurad, also known as RDEA594, is a selective uric acid re-absorption inhibitor (SURI) and is also a selective inhibitor of URAT1, a transporter in the kidney that regulates uric acid excretion from the body. RDEA594 has been shown to normalize the amount of uric acid excreted by gout patients previously classified as under-excretors. Lesinurad received FDA approval on December 22, 2015. |
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| DC75138 |
Lometrexol disodium |
Lometrexol, also known as LY264618, is a folate analog antimetabolite with antineoplastic activity. As the 6R diastereomer of 5,10-dideazatetrahydrofolate, lometrexol inhibits glycinamide ribonucleotide formyltransferase (GARFT), the enzyme that catalyzes the first step in the de novo purine biosynthetic pathway, thereby inhibiting DNA synthesis, arresting cells in the S phase of the cell cycle, and inhibiting tumor cell proliferation. The agent has been shown to be active against tumors that are resistant to the folate antagonist methotrexate. |
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| DC75139 |
Encequidar mesylate |
Encequidar, also known as HM-30181, is an oral P-glycoprotein (P-gp) inhibitor developed to enhance the oral bioavailability of P-gp substrate drugs. Encequidar showed the highest potency (IC(50)=0.63nM) among several MDR1 inhibitors, including cycloporin A, XR9576, and GF120918, and effectively blocked transepithelial transport of paclitaxel in MDCK monolayers (IC(50)=35.4nM). Encequidar is currently under clinical trials. |
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| DC75140 |
Apadoline |
Apadoline, also known as RP 60180, is a non-peptidic kappa-opioid receptor agonist. From the dose of 1 mg/kg i.v., RP 60180 slowed ECG frequency. This effect, which lasted for about 30 minutes post-injection, was most often seen at the higher doses. According to literature, both RP 60180 and pentazocine reduced pain-related CSSERP amplitudes by approximately 40%. Pentazocine tended to produce more side effects. |
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| DC75141 |
Simetride |
Simetride is used in the Reversal of resistance to vincristine in P388 leukemia. Simetride is a non-narcotic analgesic, it is an ingredient of Kyorin AP2 (a combination of Simetride and Anhydrous Caffeine (40:1)) in Japan. Kyorin AP2 is used to treat low back pain, symptomatic neuralgia, headache, menstrual pain, pharyngalgia/earache due to inflammation, toothache, postoperative pain. |
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| DC75142 |
Osilodrostat free base |
Osilodrostat, also known as LCI699, is a potent inhibitor of 11β-hydroxylase, the enzyme which catalyzes the final step of cortisol synthesis. LCI699 may thus be a potential new treatment for all forms of Cushing's syndrome. Current evidence indicates that the novel aldosterone inhibitor LCI699 is an effective and well-tolerated antihypertensive agent that lowers plasma aldosterone concentration and produces a mild ACTH-stimulated cortisol response suppressive effect. |
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| DC75143 |
Umibecestat free base |
Umibecestat, also known as CNP-520, is a beta-secretase inhibitor and is a drug candidate for prevention trials in Alzheimer's disease. CNP520 has a selectivity, pharmacodynamics, and distribution profile suitable for AD prevention studies. CNP520 reduced brain and cerebrospinal fluid (CSF) Aβ in rats and dogs, and Aβ plaque deposition in APP-transgenic mice. CNP520 reduces Aβ load and neuroinflammation in APP‐transgenic mice |
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| DC75144 |
Exatecan free base |
Exatecan, also known as DX 8951, is a semisynthetic, water-soluble derivative of camptothecin with antineoplastic activity. Exatecan mesylate inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA and inhibiting religation of DNA breaks, thereby inhibiting DNA replication and triggering apoptotic cell death. This agent does not require enzymatic activation and exhibits greater potency than camptothecin and other camptothecin analogues. |
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| DC75145 |
GS-441524 |
GS-441524 is a potent inhibitor of feline infectious peritonitis (FIP) virus with an EC50 of 0.78 μM.. GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. Note: GS-441524 is an active metabolite of Remdesivir. |
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| DC75146 |
AT-9283 free base |
AT9283 is a multikinase inhibitor, is also a small-molecule inhibitor of several kinases with potential antineoplastic activity. Multikinase inhibitor AT9283 binds to and inhibits Aurora kinases A and B, JAK2 (Janus kinase 2) and the kinase BCR-ABL, which may result in the inhibition of cellular division and proliferation and the induction of apoptosis in tumor cells that overexpress these kinases. Aurora kinases are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis; JAK2 is a kinase that transduces signals from the single chain and IL-3 cytokine receptor families, and from the IFN-gamma receptors; BCR-ABL is a fusion protein with tyrosine kinase activity that is commonly found in CML. |
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| DC75147 |
GSK-2256098 |
GSK2256098, also known as GTPL7939, is a focal adhesion kinase-1 (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. FAK inhibitor GSK2256098 inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including ERK, JNK/MAPK and PI3K/Akt, thereby inhibiting tumor cell migration, proliferation and survival, and tumor angiogenesis. The tyrosine kinase FAK is normally activated by binding to integrins in the extracellular matrix (ECM) but may be upregulated and constitutively activated in various tumor cell types. |
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| DC75148 |
Naquotinib free base |
Naquotinib, also known as ASP8273, is an orally available, irreversible, third-generation, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, ASP8273 covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. ASP8273 preferentially inhibits mutated forms of EGFR including T790M, a secondarily acquired resistance mutation, and may have therapeutic benefits in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors. |
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| DC75149 |
Pimasertib |
Pimasertib, also known as AS703026, SAR245509, MSC1936369B, is an orally bioavailable small-molecule inhibitor of MEK1 and MEK2 (MEK1/2) with potential antineoplastic activity. MEK inhibitor AS703026 selectively binds to and inhibits the activity of MEK1/2, preventing the activation of MEK1/2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. |
|
| DC75150 |
Hexamide |
Hexamide is a protein inhibitor. |
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| DC75151 |
KG-5 |
KG-5 is an orally available PDGFRß and B-Raf allosteric inhibitor. |
|
| DC75152 |
Pexmetinib |
Pexmetinib, also known as ARRY-614, is an orally bioavailable small-molecule inhibitor of p38 and Tie2 kinases with potential antineoplastic, anti-inflammatory and antiangiogenic activities. p38/Tie2 kinase inhibitor Arry-614 binds to and inhibits the activities of p38 and Tie2 kinases, which may inhibit the production of proinflammatory cytokines and may decrease tumor angiogenesis and tumor cell growth and survival. p38 is a MAP kinase that is often upregulated in cancer cells, playing a crucial part in the production of a variety of cytokines involved in inflammation and cellular proliferation such as tumor necrosis factor (TNF) and interleukin (IL)-1 and -6. Tie2 is an endothelial cell specific receptor that is activated by angiopoietins, growth factors required for angiogenesis. |
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| DC75153 |
Givinostat free base |
Givinostat or gavinostat, aslo known as ITF2357, is a potent and orally active histone deacetylase inhibitor with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities. It is a hydroxamate used in the form of its hydrochloride. Inhibition of HDAC activity by ITF2357 ameliorates joint inflammation and prevents cartilage and bone destruction in experimental arthritis.ITF2357 reduces cytokines and protects islet β cells in vivo and in vitro. ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro. |
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| DC75154 |
Cenupatide TFA |
Cenupatide is an urokinase plasminogen activator receptor (uPAR) inhibitor drug candidate. Cenupatide inhibits uPAR binding to the formyl peptide receptors (FPRs) can improve kidney lesions in a rat model of streptozotocin (STZ)-induced diabetes. Cenupatide was found to revert STZ-induced up-regulation of uPA levels and activity, while uPAR on podocytes and (s)uPAR were unaffected. In glomeruli, Cenupatide inhibited FPR2 expression suggesting that the drug may act downstream uPAR, and recovered the increased activity of the αvβ3 integrin/Rac-1 pathway indicating a major role of uPAR in regulating podocyte function. |
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