1. Cell Cycle/DNA Damage
    Autophagy
  2. CDK
    Autophagy

PHA-848125 (Synonyms: Milciclib)

Cat. No.: HY-10424 Purity: 98.61%
Data Sheet SDS Handling Instructions

PHA-848125 is a potent, dual inhibitor of CDK and Tropomyosin receptor kinase (TRK), with IC50s of 45, 150, 160, 363, 398 nM and 53 nM for cyclin A/CDK2, cyclin H/CDK7, cyclin D1/CDK4, cyclin E/CDK2, cyclin B/CDK1 and TRKA, respectively.

For research use only. We do not sell to patients.
PHA-848125 Chemical Structure

PHA-848125 Chemical Structure

CAS No. : 802539-81-7

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 264 In-stock
5 mg USD 240 In-stock
10 mg USD 396 In-stock
50 mg USD 1030 In-stock
100 mg USD 1980 In-stock
200 mg   Get quote  
500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

PHA-848125 is a potent, dual inhibitor of CDK and Tropomyosin receptor kinase (TRK), with IC50s of 45, 150, 160, 363, 398 nM and 53 nM for cyclin A/CDK2, cyclin H/CDK7, cyclin D1/CDK4, cyclin E/CDK2, cyclin B/CDK1 and TRKA, respectively.

IC50 & Target

IC50: 45 nM (cyclin A/CDK2), 150 nM (cyclin H/CDK7), 160 nM (cyclin D1/CDK4), 363 nM (cyclin E/CDK2), 398 nM (cyclin B/CDK1)[1], 53 nM (TRKA)[2]

In Vitro

PHA-848125 (0.156 or 0.625 μM) up-regulates the expression of PDCD4, DDIT4, SESN2/sestrin 2 and DEPDC6/DEPTOR in GL-Mel cells[1]. PHA-848125 potently inhibits the kinase activity of CDK2/cyclin A complex and of TRKA in a biochemical assay, with IC50s of 45 and 53 nM, respectively. PHA-848125 induces a clear accumulation of cells in G1 phase. PHA-848125 strongly inhibits NGF-induced phosphorylation of TRKA in a dose-dependent manner[2].

In Vivo

PHA-848125 (5, 10, and 15 mg/kg, p.o.) inhibits the growth of tumor in 7,12-dimethylbenz(a) anthracene (DMBA)-induced rat mammary carcinoma model. PHA-848125 has significant antitumor activity in various human xenografts and carcinogen-induced tumors as well as in disseminated primary leukemia models, with plasma concentrations in rodents in the same range as those found active in inhibiting cancer cell proliferation[2]. PHA-848125 (40 mg/kg) induces a significant tumor growth inhibition in K-RasG12DLA2 mice, and this is accompanied by a reduction in the cell membrane turnover[3].

Clinical Trial
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References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.1712 mL 10.8561 mL 21.7122 mL
5 mM 0.4342 mL 2.1712 mL 4.3424 mL
10 mM 0.2171 mL 1.0856 mL 2.1712 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[2]

Cells are seeded into 96- or 384-well plates at densities ranging from 10,000 to 30,000/cm2 in appropriate medium plus 10% FCS. After 24 hours, cells are treated in duplicate with serial dilutions of PHA-848125, and 72 hours later, viable cell number is assessed using the CellTiter-Glo Assay. IC50s are calculated using a Sigmoidal fitting algorithm. Experiments are done independently at least twice. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

PHA-848125 is formulated in glucosate.

Rats are randomized and introduced into the study when at least one mammary tumor attained a diameter of 0.5 cm. Groups of 10 animals are treated orally twice a day continuously for 10 days with vehicle (glucosate) or with 5, 10, and 15 mg/kg of PHA-848125, whereas a further group receives two cycles of PHA-848125 at 20 mg/kg orally twice a day for 5 days with an intervening rest period of 1 week. Tumor volume is measured regularly by caliper for the duration of the experiment. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

460.57

Formula

C₂₅H₃₂N₈O

CAS No.

802539-81-7

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
PHA-848125
Cat. No.:
HY-10424
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