Hedgehog pathway inhibitor (HP1-4) has been used for the inhibition of dynein ATPase in Leishmania.[1][2]
Biochem/physiol Actions
HPI-4 is a Hedgehog pathway inhibitor; ciliogenesis inhibitor.
HPI-4 is a Hedgehog pathway inhibitor; ciliogenesis inhibitor. The Hedgehog (HH) signaling pathway is targeted for anti-cancer therapeutics. A key signaling molecule in HH pathway, Smoothened (Smo), has been the target of pharmacological intervention, which has resulted in multiple Smo antagonists including Cyclopamine. However, the oncogenic form of Smo is resistant to Cyclopamine, so the identification of inhibitors of downstream effectors, such as the transcription factors Gli1 and Gli2, is important. Four small molecules were identified to inhibit HH downstream of Smo, HPI-1, HPI-2, HPI-3, and HPI-4. HPI-4 blocked HH pathway activation by SAG, decreased Smo ciliary accumulation, decreased HH activity in a consitutively active HH cell line, and decreased Gli1 and Gli2, processing, and stability. HPI-4 inhibited proliferation of cerebellar granula neuron precursor cells, an important model of HH signaling. Cilia in HPI-4-treated cells were either truncated or absent. The mechanism of action of HPI-4 is hypothesized to be directly through perturbation of ciliogenesis, leading to disruption of Gli1/Gli2 activity, which is distinctly different from that of Cyclopamine.
Journal of molecular biology, 431(19), 3787-3803 (2019-07-10)
Many medically relevant Gram-negative bacteria use the type III secretion system (T3SS) to translocate effector proteins into the host for their invasion and intracellular survival. A multi-protein complex located at the cytosolic interface of the T3SS is proposed to act
Chondrosarcoma is a type of malignant bone tumor secreting cartilage-like matrix. In clinical treatment, there is no frequently used drug treatment option except for surgical resection. Hedgehog (HH) pathway is a classical signaling pathway that regulates normal cartilage cell development.
Protein science : a publication of the Protein Society, 28(10), 1888-1901 (2019-08-09)
Translocation of virulence effector proteins through the type III secretion system (T3SS) is essential for the virulence of many medically relevant Gram-negative bacteria. The T3SS ATPases are conserved components that specifically recognize chaperone-effector complexes and energize effector secretion through the
The orientation of cell division can have important consequences on the choice of cell fates adopted by each daughter cell as well as on the architecture of the tissue within which the dividing cell resides. We have studied in detail
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