IACS-13909 is a specific and potent allosteric inhibitor of SHP2 that suppresses the signaling of RTK/MAPK pathway and overcomes multiple mechanisms underlying osimertinib resistance. IACS-13909 potently impedes the proliferation of tumors with a broad spectrum of RTKs as the oncogenic driver. Importantly, in NSCLC models with acquired resistance to osimertinib, IACS-13909 administered as a single agent or in combination with osimertinib potently reduces tumor cell proliferation in vitro and in vivo. Together, our findings provide preclinical evidence for using a SHP2 inhibitor as a therapeutic strategy in acquired EGFR inhibitor-resistant NSCLC.

Emedastine is an orally active, selective and high affinity histamine H1 receptor antagonist with a Ki value of 1.3 nM. Emedastine is a benzimidazole derivative with potent antiallergic properties and used for allergic rhinitis, allergic skin diseases and allergic conjunctivitis.

AST 487 is a RET kinase inhibitor with IC50 of 880 nM, inhibits RET autophosphorylation and activation of downstream effectors, also inhibits Flt-3 with IC50 of 520 nM.

Poseltinib (HM-71224, LY-3337641) is a potent and selective, covalent inhibitor of Btk with IC50 of 1.95 nM.

BIX01294 is a potent chemical inhibitor of G9a methyltransferase that catalyzes the mono-and di-methylation of the lysine 9 residue of histone H3. BIX01294 suppresses osteoclast differentiation on mouse macrophage-like Raw264.7 cells. BIX01294 enhances the cardiac potential of bone marrow cells.

Fasudil, a Rho-kinase inhibitor, has been shown to reduce portal venous pressure in cirrhotic rats.

Fostemsavir Tris (BMS-663068 (Tris)) is the phosphonooxymethyl prodrug of BMS-626529. Fostemsavir Tris (BMS-663068 (Tris)) is a novel attachment inhibitor that targets HIV-1 gp120 and prevents its binding to CD4+ T cells.

Lenalidomide-Br (Compound 41) is an analog of cereblon (CRBN) ligand Lenalidomide for E3 ubiquitin ligase, and is used in the recruitment of CRBN protein. Lenalidomide-Br can be connected to the ligand for protein by a linker to form PROTACs.

EST73502 is a dual μ-opioid receptor agonist and σ1 receptor antagonist with Ki of 64 nM and 118 nM, respectively.

OTS186935 trihydrochloride is a protein methyltransferase SUV39H2 inhibitor with an IC50 of 6.49 nM. OTS186935 trihydrochloride shows significant inhibition of tumor growth in mouse xenograft models without any detectable toxicity. OTS186935 trihydrochloride regulates the production of γ-H2AX in cancer cells[1].

GFB-8438 is a potent and subtype selective TRPC5 inhibitor, with IC50s of 0.18 and 0.29 μM of hTRPC5 and hTRPC4, respectively. GFB-8438 shows excellent selectivity against TRPC6, other TRP family members, NaV 1.5, as well as limited activity against the hERG channel. GFB-8438 protects mouse podocytes from injury induced by protamine sulfate model.

Encenicline hydrochloride (EVP-6124 hydrochloride) is a novel partial agonist of α7 neuronal nicotinic acetylcholine receptors (nAChRs).

LCH 7749944 (GNF-PF-2356) is a novel and potent PAK4 with IC50 of 14.93 uM, shows weak activity against other PAK family members.

DHODH-IN-11 (Compound 14b) is a Leflunomide derivative and a weak dihydroorotate dehydrogenase (DHODH) inhibitor with a pKa of 5.03[1].

SP 141 is a cell-permeable inhibitor of Mdm2 (Ki = 28 nM).

CDPPB is a potent, selective, brain penetrant positive allosteric modulator of mGlu5 receptor with EC50 of 10 nM and 20 nM for human and rat mGluR5, respectively.

LC3-mHTT-IN-AN1 (Compound AN1) is a mHTT-LC3 linker compound, which interacts with both mutant huntingtin protein (mHTT) and LC3B but not with wtHTT or irrelevant control proteins. LC3-mHTT-IN-AN1 reduces the levels of mHTT in an allele-selective manner in cultured Huntington disease (HD) mouse neurons.

Tianeptine is a selective facilitator of 5-HT uptake in vitro and in vivo.

Blasticidin S hydrochloride is a nucleoside antibiotic isolated from Streptomyces griseochromogenes. Blasticidin S is a potent inhibitor of protein synthesis in both prokaryotic and eukaryotic cells.

AAK1-IN-1(BMS-986176) is a chemical probe for AAK1 and BIKE that potently targets the ATP-binding site (AAK1 Ki = 9.1 nM; BIKE Ki = 17 nM). Regarding kinase selectivity, only three kinases were observed to bind SGC-AAK1-1 within 30-fold of the KD of AAK1 in a KINOMEscan assay (DiscoverX) at 1 μM followed by KD determinations: RIOK1 (KD = 72 nM), RIOK3 (KD = 290 nM), and PIP5K1C (KD = 260 nM). In a live cell NanoBRET assay (Promega) SGC-AAK1-1 has potency for ectopically expressed full-length AAK1- and BIKE-Nluc fusion proteins (AAK1 IC50 = 230 nM; BIKE IC50 = 1.5 μM).

ADX-102 (Reproxalap, NS-2) is a novel small molecule immunomodulator that covalently binds aldehydes including malondialdehyde and 4-hydroxynonenal, which have been shown to mediate inflammatory pain; DX-102 is a promising agent for the treatment of dry eye disease.

OTS186935 (OTS-186935) is a potent, in vivo-active inhibitor of protein methyltransferase SUV39H2 with IC50 of 6.49 nM, inhibits A549 cell growth with IC50 of 0.67 uM; causes a significant growth inhibitory effect in mouse xenograft models using MDA-MB-231 breast cancer cells as well as A549 lung cancer cells, at 25 mg/kg once daily for 14 days yielded a TGI of 60.8%; attenuates the levels of H3K9me3 in A549 xenograft mouse model.

MDI-2268 (MDI2268) is a small-molecule, in vivo-active inhibitor of plasminogen activator inhibitor type-1 (PAI-1), demonstrates excellent pharmacokinetics, potent activity against vitronectin-bound PAI-1 in vivo, and efficacy in murine model of venous thrombosis.

SIRT7 inhibitor 97491, a potent SIRT7 inhibitor with an IC50 of 325 nM, reduces deacetylase activity of SIRT7 in a dose-dependent manner. SIRT7 inhibitor 97491 prevents tumor progression by increasing p53 stability through acetylation at K373/382. SIRT7 inhibitor 97491 promotes apoptosis through caspase pathway..

UT-155 is a selective androgen receptor (AR) antagonist, with a Ki of 267 nM for AR-RBD.

AZD-7986(Brensocatib) is a highly potent, reversible, and selective DPP1 inhibitor with enzyme and cell pIC50 of 8.4.

5-Lipoxygenases (15-LO) inhibitor 1 is a heterocyclic pyrimidobenzothiazine compound that inhibits 15-LO with an IC50 value of 18 µM.

CBS-1117 is a novel fusion inhibitor with EC50 ∼3 μM against group 1 HA.

Tafluprost(AFP-168) is an anti-glaucoma prostaglandin (PG) analog.A number of 17-phenyl trinor PGF2α derivatives have been approved for the treatment of glaucoma.1,2,3,4 Of these, the ones wherein the 13,14-double bond has been hydrogenated retain relatively good potency.

Difluprednate(Durezol) is a corticosteroid, approved difluprednate for the treatment of post-operative ocular inflammation and pain.