SMYD3 inhibitor 29 is a highly potent, selective, covalent inhibitor of histone methyltransferase SMYD3 with IC50 of 11.7 nM.SMYD3 inhibitor 29 exhibits high potency by inhibiting SMYD3's enzymatic activity and showing antiproliferative activity against HepG2 in 3D cell culture (GI50=1.04 uM).SMYD3 inhibitor 29 inhibits cellular MAP3K2 methylation.SMYD3 inhibitor 29 displayed high selectivity when tested against a panel of methyltransferases, namely, SMYD1-2, G9a, PRDM9, and PRMT5.

SMIP-30 is a potent and selective inhibitor of PPM1A with IC50 of 1 uM, selectively inhibits the phosphatase activity of PPM1A.SMIP-30 shows poor inhibitory activity against closest homolog PPM1B (IC50>30 uM).SMIP-30 is an uncompetitive inhibitor for PPM1A (Ki=0.84 uM), does not exhibit any cytotoxic effects up to 30 uM in THP-1 macrophages.SMIP-30 dose-dependently reduces the Mtb burden in infected macrophages, and is well tolerated in vivo and combined with rifampicin reduces Mtb burden in the lungs of infected mice.SMIP-30 induces LC3B-II expression, activates autophagy in Mtb-infected macrophages in a PPM1A-dependent manner.SMIP-30 induces a dose-dependent increase in phosphorylation of S403-p62 in WT macrophages.

SKI-73 is a CARM1 chemical probe with pro-drug properties, can readily penetrate cell membranes and then be processed into two active CARM1 inhibitors.SKI-73 (10 uM) fully suppresses the methylation of BAF155 Arg1064 in MCF-7 cells.SKI-73 inhibits in vitro invasion but not proliferation of breast cancer cells ( MDA-MB-231 cell, EC50=1.3 uM).SKI-73 recapitulates the anti-invasion effect of the genetic perturbation of CARM1.Either CARM1 knockout or CARM1 inhibition with SKI-73 alters the epigenetic plasticity in a proliferation-independent manner by replacing the most invasion-prone subpopulation with the non-invasive subpopulation(s) to suppress the invasive phenotype.

SJ018 (SJ-018) is a potent, highly selective BET BD2 inhibitor with Kd of 14 nM (BRD2-BD2), 67-fold selectivity over BRD2-BD1. SJ018 is more effective than JQ1 in increasing FRAP in cells, potently inhibits MV4-11 cell growth with GI50 of 2-3 nM (Days3-7).

SIRT6 activator CL5D is a novel small-molecule activator of SIRT6 deacetylation, stimulates 4-fold activation of SIRT6 (1 uM) against H3K9ac (20 uM) at 3 uM.CL5D demonstrate competitive inhibition with Ki of 13.4 uM.CL5D exhibited time-dependent deacetylation at H3K9 by SIRT6 in HEK293T cells.

SIRT5 inhibitor 32 is an efficient, cellularly active small molecule that targets SIRT5.SIRT5 inhibitor 32 inhibits cell growth of SIRT5-dependent AML cell lines SKM-1, OCIAML2 and MOLM-13 with IC50 of 9, 20, and 24 uM, respectively.SIRT5 inhibitor 32 is also shown to inhibit SIRT5 in HeLa cells by using an assay that produce in-cell fluoresence in response to SIRT5 activity in the mitochondria.SIRT5 inhibitor 32 displays cytoselective toxicity towards SIRT5-dependent AML cells (SKM-1) over HEK293T cells in culture.

SIRT3 inhibitor 8 is a SIRT3 selective inhibitor with IC50 of 6 uM, 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2.SIRT3 inhibitor 8 reduced DLBCL cell viability and triggered activation of autophagy.

SIRT2 inhibitor 56 is a potent selective SIRT2 inhibitor with IC50 of 780 nM.SIRT2 inhibitor 56 displays >300 to >800-fold selectivity over SIRT1 and 3, respectively.SIRT2 inhibitor 56 dose-dependently increases tubulin acetylation in treated non-small cell lung cancer cell line NCI-H460.SIRT2 inhibitor 56 shows cytotoxicity in in B-cell lymphoma and other cancer cell lines (Raji cell IC50=9.1 uM).SIRT2 inhibitor 56 induces apoptosis and shows anti-proliferation effect in OCI-Ly8-LAM53 (OCI) cells.

SIRT2 inhibitor 55 is a potent and selective SIRT2 inhibitor with IC50 of 250 nM.SIRT2 inhibitor 55 displays >300 to >800-fold selectivity over SIRT1 and 3, respectively.SIRT2 inhibitor 55 dose-dependently increases tubulin acetylation in treated non-small cell lung cancer cell line NCI-H460.SIRT2 inhibitor 55 shows cytotoxicity in in B-cell lymphoma and other cancer cell lines (Raji cell IC50=11.9 uM).

SI-109 (SI 109) is a selective, high-affinity and cell-permeable STAT3 SH2 domain inhibitor with Ki of 9 nM, component of STAT3 degrader SD-36 (PROTAC).

SHP2 PROTAC R1-5C is a potent and highly selective SHP2 PROTAC created by conjugating RMC-4550 with pomalidomide using a PEG linker, with a low nanomolar DC50; SHP2 PROTAC R1-5C is highly selective for SHP2, induces degradation of SHP2 in leukemic cells at submicromolar concentrations. SHP2 PROTAC R1-5C inhibits MAPK signaling, and suppresses cancer cell growth. SHP2 PROTACs serve as an alternative strategy for targeting ERK-dependent cancers and are useful tools alongside allosteric inhibitors for dissecting the mechanisms by which SHP2 exerts its oncogenic activity.

SH045 (SH-045, Larixyl-6-N-methylcarbamate) is a potent, selective TRPC6 antagonist (blocker) with IC50 of 63 nM.SH045 displays 13-fold subtype selectivity over TRPC3 in stably expressing HEK293 cells.Treatment of isolated perfused lung preparations with SH045 led to a decrease in lung ischemia-reperfusion edema (LIRE), a life-threatening condition associated with TRPC6 that may occur after organ transplantation.

SGC-STK17B-1 is a potent, selective, ATP-competitive inhibitor of death-associated protein kinase family member STK17B (DRAK2) with IC50 of 34 nM, >100-fold selectivity over STK17A; SGC-STK17B-1 is also >100-fold selective over all of the other kinases tested, with only STK17A, CAMKK1, and AURKB (IC50s=5-9 uM) in panel of 403 wild type human kinase assays. SGC-STK17B-1 demonstrated the highest cell potency in the NanoBRET target engagement assay (IC50=190 nM). SGC-STK17B-1 is the first truly potent and selective chemical probe of STK17B.

SGC8158 (SGC-8158) is a potent, selective, and SAM-competitive inhibitor of PRMT7 with IC50 of <2.5 nM, the active component of it's cell permeable prodrug SGC3027.

SGC6870N is the negative control of SGC-6870 (R-isomer), which is a potent, selective, cell-active PRMT6 inhibitor.

SGC6870 (SGC-6870 (R-isomer)) is a potent, selective, cell-active PRMT6 inhibitor with IC50 of 77 nM.SGC6870 displays outstanding selectivity for PRMT6 over a broad panel of other methyltransferases and nonepigenetic targets.SGC6870 binds to a unique, induced allosteric pocket of PRMT6.SGC6870 engages PRMT6 and potently inhibits its methyltransferase activity in cells.SGC6870 is a well-characterized PRMT6 chemical probe and a valuable tool for further investigating PRMT6 functions in health and disease.

SGC3027N (SGC-3027N) is a negative control compound for SGC3027, shows markedly less potent (14 uM) against PRMT7 and other protein methyltransferases.

SF-3-030 is a novel ATP-dependent/catalytic site inhibitor of ERK1/2, inhibits A375 cell viability with IC50 of 4.9 uM.SF-3-030 showed selective inhibition of cancer cell lines with activating mutations in the ERK1/2 pathway.SF-3-030 inhibited viability of four melanoma cell lines containing either BRAF or NRas mutations with IC50 of 5-10 uM.SF-3-030 selectively regulates ERK-dependent immediate early gene expression, causes differential changes in AP-1 protein levels characterized by inhibition of Fra-1, FosB, and the alternative splice variant FosB2 but no effect on c-Fos levels, and induces ROS mediates inhibition of A375 cell proliferation.

SEW84 (SEW04784) is a first-in-class, specific inhibitor of the Aha1-stimulated Hsp90 (ASH) ATPase activity (IC50=0.3 uM) without inhibiting basal Hsp90 ATPase; SEW84 binds to the C-terminal domain of Aha1 (Kd=1.7 uM) to weaken its asymmetric binding to Hsp90. SEW84 inhibited the GR- and AR-dependent luciferase expression with IC50 of 1.3 uM and 0.7 uM respectively. SEW84 blocks Aha1-dependent Hsp90 chaperoning activities, including the in vitro and in vivo refolding of firefly luciferase, and the transcriptional activity of the androgen receptor in cell-based models of prostate cancer. SEW84 promotes the clearance of phosphorylated tau in cellular and tissue models of neurodegenerative tauopathy.

sCSF1Rinh is a CNS-penetrant, potent and selective small-molecule CSF1R inhibitor, binds to CSF1R in a DFG-out conformation.is highly selective for CSF1R as compared to other kinases with a selectivity score of S(35)=0.005, sCSF1Rinh exhibited excellent pharmacokinetic properties including good oral bioavailability and CNS penetrance.sCSF1Rinh (500 nM) blocks these phosphorylation events in CSF1 (100 ng/mL) stimulation of BV2 microglia.sCSF1Rinh inhibited murine bone marrow-derived macrophage proliferation with IC50 of 22 nM, sCSF1Rinh significantly depletes microglia in a concentration-dependent manner in murine mixed glial cultures (IC50=188 nM).sCSF1Rinh reduced the number of microglia and infiltrating macrophages in an acute LPS model, with diminished microglial/macrophage proliferation and attenuated inflammatory response.sCSF1Rinh also suppressed a deleterious microglial response in the C57BL/6 EAE (experimental autoimmune encephalomy) model as well as the MOG peptide-induced non-obese diabetic EAE model of progressive MS (NOD-EAE) and improved neurological impairments in both models.

SCR7 is a specific inhibitor of nonhomologous end-joining (NHEJ), blocks Ligase IV-mediated joining by interfering with its DNA binding but not that of T4 DNA Ligase or Ligase I; inhibits NHEJ in a Ligase IV-dependent manner within cells, causes accumulation of double-strand breaks (DSBs), and activates the intrinsic apoptotic pathway; decreases cell proliferation of MCF7, A549, and HeLa with IC50 of 40, 34, and 44 uM, respectively; increases the efficacy of DSB-inducing therapeutic modalities in mouse xenografts; increases the efficiency of precise genome editing with CRISPR-Cas9 in mammalian cell lines and in mice.

SCP1 inhibitor T-65 (T-65) is a specific, small molecule covalent inhibitor of small CTD phosphatase 1 (SCP1), reduces transcription factor REST protein level HEK293 cells with EC50 of 1.5 uM.T-65 showed no detectable inhibition against a panel of eight mammalian cysteine-based phosphatases, including SHP2, TCPTP, CD45, DUSP3 and and lymphoid protein tyrosine phosphatase (LYP) at 25 uM.T-65 promotes REST degradation, increases expression of REST-suppressed genes DYRK1a, ELAVL1, USP37, CELSR3, and SCN2 in HEK293 cells.

SCP1 inhibitor T-62 (T-62) is a specific, small molecule covalent inhibitor of small CTD phosphatase 1 (SCP1), reduces transcription factor REST protein level HEK293 cells.

SC-78080 (SD-2590) is a potent, selective inhibitor of MMP2/9/13 with IC50 of <0.1/0.18/<0.1 nM, respectively.SC-78080 shows weaken inhibitory effect on MMP3/8, and no inhibition on MMP1/7.

SBI-4668 (SBI 4668) is a novel furanylbenzamide molecule as inhibitor of both WT and oncogenic SHP2 with IC50 of 0.73/1.8 uM for Wt SHP2/SHP2-E76K, 13-fold selective over PTP1B and 73-fold selective over STEP; SBI-4668 exhibited cell viability inhibitory effect on cell growth in both Kasumi-1 cells (IC50=8.5 uM) and KYSE-520 cells (IC50=5.4 uM), SBI-4668 on cell viability was also determined in additional AML cell lines, including MOLM-13 (IC50 = 12 μM) and MV4-11 (IC50 = 8.2 μM). SBI-4668 inhibited U-937 cell (harbor a G60R oncogenic mutation in SHP2) growth with IC50 of 6.3 uM, which is comparable to the potency found in AML cells expressing WT SHP2, while RMC4550 showed a very weak effect on this G60R mutation cell.

SBI-2130 (SBI 2130) is a novel furanylbenzamide molecule as inhibitor of both WT and oncogenic SHP2 with IC50 of 0.22/5.0 uM for Wt SHP2/SHP2-E76K.

SBI-0797750 (SBI 0797750) is a potent, fully selective PfGluPho inhibitor with robust nanomolar activity against recombinant PfGluPho, PvG6PD, and P. falciparum blood-stage parasites.SBI-0797750 disturbs the cytosolic glutathione-dependent redox potential, as well as the cytosolic and mitochondrial H2O2 homeostasis of P. falciparum blood stages, at low nanomolar concentrations.SBI-0797750 does not harm red blood cell (RBC) integrity and phagocytosis and thus does not promote anemia.

SBI-0637142 is a potent Smac mimetic that preferentially targets BIRC2, latency-reversing agent (LRA), specifically and potently promote HIV-1 latency reversal activity.SBI-0637142 modestly induced HIV-1 latency ex vivo in CD4+ T cells from ART-suppressed aviremic HIV-infected patients as a single agent, showed robust activity when administered in combination with the HDACi panobinostat.SBI-0637142's latency reversal activity is dependent on the NIK-dependent NF-κB signaling.

S2C3 is a small molecule HIV-1 fusion inhibitor, targets the membrane proximal external region (MPER) of HIV-1 envelope spike.S2C3 interacted with gp41-inter with an affinity of 2.0 uM.S2C3 has been shown to effectively block binding to the intact HIV-1 Env expressed on the cell surface by soluble CD4 but not by CD4 binding the sitedirected NAb VRC01, or the prefusion conformation-specific NAb PG16.S2C3 targets a site in the HIV-1 Env distinct from sites targeted by small-molecule entry inhibitors that have been identified so far.S2C3 could stabilize HIV-1 Env in the prefusion conformation, making it potentially useful in a vaccine preparation to reduce the conformational flexibility of Env.

S1g-2 (Hsp70-Bim inhibitor S1g-2) is a selective inhibitor to block interactions of Hsp70-Bim with IC50 of 0.4 uM in FPA assays, > 40-fold selectivity to target Hsp70-Bim over Bcl-2-Bim. S1g-2 induces cell-type-specific apoptosis in CML cells through selectively disrupting the Hsp70-Bim PPI. S1g-2 progressively enhanced lethality along with the increase in BCR-ABL-independent TKI resistance in the K562 cell lines. S1g-2 is more effective in primary samples from BCR-ABL-independent TKI-resistant patients than those from TKI-sensitive patients.