hedgehog pathway inhibitor

LGE-899 (Sonidegib metabolite M48) 是 Sonidegib 的主要代谢物，是一种刺猬通路抑制剂。 LGE-899 (60 h) 的 Tmax 比 Sonidegib 长得多。

RU-SKI 43 是一种有效的选择性刺猬酰基转移酶 (Hhat) 抑制剂，IC50 为 850 nM。RU-SKI 43 具有抗癌活性，是治疗肺腺癌的潜在化合物。RU-SKI 43 通过独立于平滑化的非规范信号传导降低 Gli-1 激活，并抑制 Akt 和 mTOR 通路活性。

CUR61414 是 Hedgehog 信号通路的细胞渗透性抑制剂 (IC50 = 100-200 nM)，并选择性地结合 smoothened (Ki = 44 nM)。

CUR61414 hydrochloride 是属于氨基脯氨酸类化合物的小分子。CUR61414 hydrochloride 是一种细胞渗透性的 Hedgehog 信号通路抑制剂(IC50= 100-200 nM)，可选择性结合 Smoothened (Smo, Ki= 44 nM)。CUR61414 hydrochloride 可以诱导癌细胞凋亡 (apoptosis) 而不影响非癌症细胞。

Itraconazole (R51211) 属于三唑类天然产物，是一种抗真菌剂，具有口服活性。Itraconazole 是一种 Hedgehog 信号通路拮抗剂，一种 oxysterol-binding protein (OSBP) 抑制剂，也是一种细胞色素 P-450 依赖性酶的抑制剂。

Vismodegib (GDC-0449) 是一种刺猬抑制剂，IC50值为 3 nM。它还可抑制 P-gp 和ABCG2的活性，IC50值分别为 3.0 μM 和 1.4 μM。

HhAntag 是高效的、特异性的、具有口服活性的 Hh 通路的SMO 拮抗剂。

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

HedgehogIN-7 (Compound 8g)，这是一种针对Hedgehog通路的嘌呤衍生抑制剂，可有效抑制Hedgehog信号传导并降低其基因表达。在胰腺癌细胞线Mia-PaCa-2中，HedgehogIN-7 显示出了显著的细胞毒性和高度选择性，因此适用于胰腺癌的相关研究。

SMO-IN-5 ((Compound 25(B31)) 作为一种有效的smoothened (SMO) 抑制剂，能够抑制Hedgehog (Hh) 信号通路，并通过抑制细胞增殖并诱导细胞凋亡 (Apoptosis) 来发挥其作用。此外，SMO-IN-5 还表现出抗肿瘤活性。

HPI 1 是一种刺猬 (Hh) 信号抑制剂。在 Shh-LIGHT2 细胞中抑制 Sonic Hedgehog (Shh)-、SAG- 和 Gli 诱导的 Hh 通路激活（Shh-、SAG-、Gli2- 和 Gli1 诱导的激活的 IC50 值为 1.5、1.5、4 和 6 μM） .

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

Ciliobrevin A (HPI-4) 是Hedgehog(Hh) 信号通路抑制剂，平均抑制浓度 (IC50) 值小于 10 μM。

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)

JK184 是 Hedgehog 抑制剂，在哺乳动物细胞中的IC50值为 30 nM。

Saikosaponin B1 是柴胡的生物活性成分，具有抗癌作用。它能够靶向SMO 抑制 Hedgehog 通路，显著抑制髓母细胞瘤模型中的肿瘤生长。

PF-5274857 (PF-5274857 free base) freebase 是有效的、具有口服活性的、选择性的、可透过血脑屏障的 Smo 拮抗剂，其 IC50=5.8 nM，Ki=4.6 nM。它有用于包括激活的 Hh 途径驱动的脑肿瘤和脑转移在内的多种肿瘤的研究潜力。

SMO-IN-3 是 smoothened (SMO) 对有效抑制剂，能够作用于 hedgehog (Hh) 信号通路 (IC50: 34.09 nM)。SMO-IN-3 能够抑制人髓母细胞瘤细胞系 Daoy 的增殖，表现出抗癌作用。

MK-4101 是一种 SMO 拮抗剂 ，对 293 细胞的 IC50为 1.1 µM。它也是一种 hedgehog 信号通路的有效抑制剂 ，对小鼠细胞和KYSE180 食管癌细胞的IC50分别为 1.5 µM 和 1 µM。它能抗肿瘤，抑制肿瘤细胞增殖并诱导细胞凋亡。

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.

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

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.

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

3-epi-Vitamin D3 (Epicholecalciferol) 是维生素 D3 类似物，是一种Hedgehogpathway 抑制剂，在U87MG 细胞中测定的IC50为 39.2 μM。