hedgehog pathway inhibitor

Wnt pathway inhibitor 4 is a small molecule antimicrobial agent with antibacterial and antiproliferative activity against cancer cells.

Wnt pathway inhibitor 3 is a potent AC1 inhibitor with an IC50 value of 45 nM.Wnt pathway inhibitor 3 has antiproliferative activity and can be used in studies to ameliorate osteoarthritis in a mouse model of experimental osteoarthritis.

Ciliobrevin A (HPI-4) is an inhibitor of hedgehog signaling pathway with an IC50 <10 μM.

Vismodegib (GDC-0449) is a hedgehog pathway inhibitor (IC50: 3 nM). It also inhibits P-gp (IC50: 3.0 μM), ABCG2 (IC50: 1.4 μM).

CUR61414 hydrochloride is a potent and cell permeable inhibitor of Hedgehog signaling pathway (IC50 =100-200 nM). CUR61414 hydrochloride is a small-molecule aminoproline class compound. CUR61414 hydrochloride selectively binds to smoothened (Smo, Ki= 44 nM). CUR61414 hydrochloride can induce cancer cells apoptosis without affecting neighboring non-tumor cells.

RU-SKI 43 is a potent and selective hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 850 nM.RU-SKI 43 has anticancer activity and is a potential compound for the treatment of lung adenocarcinomas.RU-SKI 43 reduces Gli-1 activation through smoothing-independent non-canonical signalling and inhibits Akt and mTOR pathway activity.

LGE-899 (Sonidegib metabolite M48) is a main metabolite of Sonidegib which is an inhibitor of the hedgehog pathway. The Tmax of LGE-899(60 h) is much longer than Sonidegib.

CUR61414 is a cell-permeable inhibitor of Hedgehog signaling pathway (IC50 =100-200 nM) and selectively binds to smoothened (Ki = 44 nM).

Itraconazole (R51211) is a triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes required for ERGOSTEROL synthesis.

HhAntag is a small molecule inhibitor of GLI1-mediated transcription, an essential down-stream element of the Hedgehog (Hh) pathway with the anti-tumor activity.

HPI-1 (hydrate) is a Hedgehog (Hh) pathway inhibitor that suppresses signaling through Sonic Hh (IC50= 1.5 μM) without significantly affecting Wnt signaling (IC50≥ 30 μM).1HPI-1 suppresses Hh activation induced by loss of Suppressor of Fused or by Gli overexpression, suggesting action at posttranslational modification of Gli protein or at the interaction of Gli with a co-factor.1HPI-1 (hydrate) also inhibits signaling through the oncogenic Smoothened (Smo) mutant SmoM2 in neuron precursors, preventing cell proliferation.1 1.Hyman, J.M., Firestone, A.J., Heine, V.M., et al.Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockadeProceedings of the National Academy of Sciences of the United States of America106(33)14132-14137(2009)

PF-5274857 (PF-5274857 free base) is an effective and selective hedgehog signaling pathway inhibitor (IC50: 5.8 nM and a Ki: 4.6 nM). PF-5274857 is a potentially attractive clinical candidate for the treatment of tumor types including brain tumors and brain metastasis driven by an activated Hh pathway.PF-5274857 was found to effectively penetrate the blood-brain barrier and inhibit Smo activity in the brain of primary medulloblastoma mice, resulting in improved animal survival rates. PF-5274857 was orally available and metabolically stable in vivo.

Saridegib is an effective and specific inhibitor of Smoothened and a key signaling transmembrane protein in the Hedgehog pathway.

Glasdegib hydrochloride is a small-molecule inhibitor of the Hedgehog (Hh) signaling pathway with potential antineoplastic activity.

Vismodegib-d7 is a deuterated compound of Vismodegib. Vismodegib has a CAS number of 879085-55-9. Vismodegib is a hedgehog pathway inhibitor (IC50: 3 nM). It also inhibits P-gp (IC50: 3.0 μM), ABCG2 (IC50: 1.4 μM).

HPP-9, a Proteolysis-Targeting Chimera (PROTAC) derived from Hedgehog Pathway Inhibitor-1 (HPI-1) with a pIC50 value of 6.71, is designed to degrade BET bromodomains and exhibits antitumor activity [1].

NL-103 is a novel dual-targeted inhibitor of histone deacetylases and hedgehog pathway, effectively overcomes vismodegib resistance conferred by Smo mutations. NL-103 comprises structural elements of Hh pathway inhibitor vismodegib, and histone deacetylase (HDAC) inhibitor vorinostat. NL-103 simultaneously and significantly inhibited both HDACs and Hh pathway. Importantly, NL-103 effectively overcame vismodegib resistance induced by Smoothened point mutations. Moreover, NL-103 significantly downregulated the expression of Gli2 which plays an important role in Hh pathway. NL-103 may be a promising compound for clinical development as a more effective Hh pathway inhibitor.

Patidegip, laos known as Saridegib and IPI-926, is an orally bioavailable, cyclopamine-derived (for structure comparison see Fig 1) inhibitor of the Hedgehog (Hh) pathway with potential antineoplastic activity. Specifically, Hedgehog pathway inhibitor IPI-926 binds to and inhibits the cell membrane-spanning G-protein coupled receptor SMO, which may result in the suppression of Hh pathway signaling and a decrease in tumor cell proliferation and survival. SMO is activated upon binding of Hh ligand to the cell surface receptor Patched (PTCH); inappropriate activation of Hh signaling and uncontrolled cellular proliferation may be associated with SMO mutations.

SMO-IN-3 is a potent inhibitor of smoothened (SMO) that acts on the hedgehog (Hh) signaling pathway (IC50: 34.09 nM). SMO-IN-3 inhibits the proliferation of Daoy, a human medulloblastoma cell line, and exhibits anticancer effects.

MK-4101, an effective inhibitor of the Hedgehog pathway, has anti-tumor activity through the induction of extensive apoptosis and inhibition of proliferation in tumor cells.

Hedgehog IN-2 (Compound 20) functions as an inhibitor of the Hedgehog signaling pathway, exhibiting an IC50 of <0.003 μM in C3H10T1/2 cells [1].

HPI 1 is a hedgehog (Hh) signaling inhibitor. Inhibits Sonic hedgehog (Shh)-, SAG- and Gli-induced Hh pathway activation in Shh-LIGHT2 cells (IC50 values are 1.5, 1.5, 4, and 6 μM for Shh-, SAG-, Gli2- and Gli1-induced activation).

PF-5274857 is a potent, orally active and selective inhibitor of hedgehog (Hh) signaling pathway (IC50 = 5.8 nM, Ki = 4.6 nM) . PF-5274857 effectively penetrates the blood-brain barrier and inhibits Smo activity in the brain of primary medulloblastoma mic

3-epi-Vitamin D3 (Epicholecalciferol), an analogue of Vitamin D3, serves as a Hedgehog pathway inhibitor, exhibiting potency with an IC50 value of 39.2 μM in U87MG cells.

JK184 is a potent Hedgehog (Hh) pathway inhibitor.

Vismodegib-d4 is a deuterated compound of Vismodegib. Vismodegib has a CAS number of 879085-55-9. Vismodegib is a hedgehog pathway inhibitor (IC50: 3 nM). It also inhibits P-gp (IC50: 3.0 μM), ABCG2 (IC50: 1.4 μM).

Hedgehog IN-3 (compound 3), with an IC50 value of 0.01 µM, serves as a hedgehog pathway inhibitor, proving beneficial for cancer research applications [1].

M-25 is a Smoothened antagonist and inhibitor of the Hedgehog pathway.

Saponin activator. Activates release of Prostaglandin E2 in vitro. Anti-inflammatory agent. Orally active. Active in vivo and in vitro.