HPI-4,Hedgehog Pathway Inhibitor 4 Property

Boiling point:

564.5±50.0 °C(Predicted)

Density 

1.471±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble10mg/mL, clear

pka

6.46±0.20(Predicted)

form 

powder

color 

off-white, off-white to orange

Safety

Hazard Codes 

Xn,N

Risk Statements 

22-50/53

Safety Statements 

60-61

RIDADR 

UN 3077 9 / PGIII

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P273Avoid release to the environment.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P391Collect spillage. Hazardous to the aquatic environment

P501Dispose of contents/container to..…

HPI-4,Hedgehog Pathway Inhibitor 4 Chemical Properties,Usage,Production

Description

Ciliobrevin A is a hedgehog pathway inhibitor that blocks sonic hedgehog (Shh)-induced hedgehog pathway activation (IC₅₀ = 7 μM). It disrupts primary cilia formation and inhibits the dynein-dependent microtubial gliding and ATPase activities of the cytoplasmic ATPases associated with various cellular activities (AAA+) family. Ciliobrevin A also inhibits mammalian target of rapamycin complex 1 (mTORC1) activity in uninfected and human cytomegalovirus (HCMV)-infected cells, suggesting that mTORC1 activation requires dynein-dependent transport for cellular activation.

Uses

Ciliobrevin A is a Hedgehog pathway inhibitor; ciliogenesis inhibitor. The Hedgehog (HH) signaling pathway is targeted for anti-cancer therapeutics. Ciliobrevin A inhibited proliferation of cerebellar granula neuron precursor cells, an important model of HH signaling.

Uses

Hedgehog pathway inhibitor (HP1-4) has been used for the inhibition of dynein ATPase in Leishmania.

Biochem/physiol Actions

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.

storage

Store at +4°C