MAPK

SHP2-IN-38 is an innovative green fluorescent inhibitor targeting SHP2, exhibiting IC50 values as follows: 2.89 μM (SHP2), 8.73 μM (SHP1), 11.08 μM (PTP1B), and 33.07 μM (TCPTP). It impedes the SHP2-mediated ERK signaling pathway and inhibits MV4-11 cell proliferation in vitro with an IC50 of 7.90 μM. The excitation wavelength of SHP2-IN-38 is 360 nm, with a maximum emission wavelength of 550 nm in DMSO and 540 nm in DMF. Additionally, it demonstrates green fluorescent imaging in HeLa cells and zebrafish.

NK7-902 is a CRBN molecular glue degrader of NEK7. It fully degrades NEK7 in human primary monocytes and whole blood, yet only partially inhibits NLRP3-dependent IL-1β production. NK7-902 results in profound and lasting degradation of NEK7, but only temporarily blocks NLRP3 inflammasome activation in non-human primates via oral administration. The compound demonstrates activity in mouse systems.

KRAS Inhibitor-38 (Example 18) is a potent inhibitor capable of effectively suppressing the activity of KRAS G12C, KRAS G12D, and KRAS G12V in vivo.

KRAS G12C inhibitor 18 is a potent, orally active compound that inhibits KRAS G12C and exhibits anti-tumor activities.

PROTAC MEK1 Degrader-1, a targeted protein degradation agent, combines a MEK1 inhibitor with a von Hippel-Lindau ligand to effectively inhibit ERK1/2

KRAS inhibitor-33 (compound 115a) is a pyrido[2,3-d]pyrimidine derivative that serves as an effective inhibitor of KRAS, exhibiting an IC50 value of ≤ 100nM.

PROTAC KRAS G12C degrader-1, a cereblon-based degrader, promotes CRBN/KRAS G12C dimerization and facilitates the degradation of GFP-KRAS G12C in reporter cells

SW083688 is a potent and highly selective inhibitor of Thousand-And-One Kinase 2 (TAOK2) with an IC 50 value of 1.3 µmol/L.

DS03090629, an orally active MEK inhibitor, functions by competitively inhibiting MEK activity in the presence of ATP. This compound demonstrates strong binding affinity to both MEK and phosphorylated MEK, with dissociation constants (Kd) of 0.11 and 0.15 nM, respectively. It has shown efficacy in suppressing the proliferation of melanoma cell lines that overexpress BRAF mutations, achieving IC50 values of 74.3 and 97.8 nM for BRAF V600E and MEK1 F53L transfected A375 cells, respectively. DS03090629 is thus considered promising for anti-melanoma therapies.

KRAS G12D inhibitor 17, a quinazoline-linked prolinamide, degrades mutant KRAS protein; a PROTAC.

MEK/RAF-IN-1 (Compound 16b) serves as an inhibitor targeting both MEK and RAF, demonstrating potent efficacy with IC 50 values reported at 28 nM for MEK1, and 3 nM for both BRAF and BRAFV600E. This compound exhibits significant antitumor capabilities, effectively curbing cell proliferation in vitro in MIA PaCa-2 (G12C KRAS), HCT116 (G13D KRAS), and C26 (G12D KRAS) cells. Furthermore, MEK/RAF-IN-1 significantly restricts tumor growth in xenograft mouse models employed in the study of colorectal cancer.

Cobimetinib R-enantiomer is the less active R-enantiomer of Cobimetinib which is a selective MEK inhibitor.

(RS)-G12Di-1 is a selective covalent inhibitor of K-Ras-G12D.

HPK1-IN-8 is an allosteric, inactive, conformation-selective triazolopyrimidine ketone HPK1 inhibitor.

ADT-007 is a pan-RAS inhibitor with potent anticancer activity.

RTIL 13 inhibits dynamin GTPase (IC50: 2.3 μM), targets its lipid binding domain, and suppresses endocytosis (IC50: 9.3 & 7.1 μM).

Ibetazol is an inhibitor of importin β1 (KPNB1), which functions by binding to Cys585 of importin β1, thus preventing importin β1-mediated nuclear import with an EC50 of 6.1 µM.

MRTX849 analog 24, a KRAS G12C inhibitor with an alkyne for click probes, aids in studying MRTX849's functionality.

HSND80 (Compound 1) is an orally active MNK/p70S6K inhibitor, exhibiting a Kd value of 44 nM for MNK1 and 4 nM for MNK2. The residence time of HSND80 on MNK1 and MNK2 is 45 minutes and 58 minutes, respectively. HSND80 effectively inhibits non-small cell lung cancer (NSCLC) both in vitro and in vivo, and suppresses the growth of triple-negative breast cancer (TNBC) cells in vitro.

(S)-BAY-293 is a potent pan-KRAS inhibitor for the study of primary non-small lung and pancreatic cancers.