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

Milciclib (Synonyms: PHA-848125)

Cat. No.: HY-10424 Purity: 98.61%
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.

Milciclib Chemical Structure

Milciclib 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
Estimated Time of Arrival: December 31
5 mg USD 240 In-stock
Estimated Time of Arrival: December 31
10 mg USD 396 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1030 In-stock
Estimated Time of Arrival: December 31
100 mg USD 1980 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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    Milciclib purchased from MCE. Usage Cited in: Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.

    Western blot analysis of selected MAPK and AKT/mTOR pathway components in Trametinib- and Temsirolimus-treated cells.

    Milciclib purchased from MCE. Usage Cited in: Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.

    Western blot analysis of selected MAPK and AKT/mTOR pathway components in Trametinib- and Temsirolimus-treated cells.
    • 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
    Solvent & Solubility
    In Vitro: 

    10 mM in DMSO

    Preparing
    Stock Solutions
    Concentration Solvent 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.
    References
    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]

    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

    SMILES

    O=C(NC)C1=NN(C2=C1C(C)(CC3=CN=C(N=C23)NC4=CC=C(C=C4)N5CCN(CC5)C)C)C

    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

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    Product Name:
    Milciclib
    Cat. No.:
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    Cat. No.: HY-10424