Milciclib (Synonyms: PHA-848125)

Cat. No.: HY-10424 Purity: 99.44%: FAQs
Data Sheet SDS COA Handling Instructions

Milciclib (PHA-848125) is a potent, ATP-competitive and 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

CAS No. : 802539-81-7

Size	Price	Stock	Quantity
Solution
10 mM * 1 mL in DMSO	USD 264	In-stock	Estimated Time of Arrival: December 31
Solid + Solvent
10 mM * 1 mL ready for reconstitution	USD 264	In-stock	Estimated Time of Arrival: December 31
Solid
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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This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 5 publication(s) in Google Scholar

5 Publications Citing Use of MCE Milciclib

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Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target^[1]

cyclin A/CDK2

45 nM (IC₅₀)

cyclin E/CDK2

363 nM (IC₅₀)

cyclin H/CDK7

150 nM (IC₅₀)

cyclin D1/CDK4

160 nM (IC₅₀)

cyclin B/CDK1

398 nM (IC₅₀)

TRKA

53 nM (IC₅₀)

In Vitro

Milciclib (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]. Milciclib (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. Milciclib induces a clear accumulation of cells in G1 phase. Milciclib strongly inhibits NGF-induced phosphorylation of TRKA in a dose-dependent manner^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Milciclib (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. Milciclib 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]. Milciclib (PHA-848125; 40 mg/kg) induces a significant tumor growth inhibition in K-Ras^G12DLA2 mice, and this is accompanied by a reduction in the cell membrane turnover^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

460.57

Appearance

Solid

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

In Vitro:

DMSO : 20 mg/mL (43.42 mM; Need ultrasonic)

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.

In Vivo:

1.

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2 mg/mL (4.34 mM); Clear solution
2.

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2 mg/mL (4.34 mM); Clear solution

*All of the co-solvents are available by MCE.

Purity & Documentation

Purity: 99.89%

Select Batch:

Data Sheet (279 KB) SDS (251 KB)

COA (246 KB) HNMR (274 KB) LCMS (98 KB)

Handling Instructions (2659 KB)

References

[1]. Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, Del Bufalo D, Desideri M, Bonmassar E, Pfeffer U, D'Atri S. Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhib [Content Brief]

[2]. Albanese C, Alzani R, Amboldi N, Avanzi N, Ballinari D, Brasca MG, Festuccia C, Fiorentini F, Locatelli G, Pastori W, Patton V, Roletto F, Colotta F, Galvani A, Isacchi A, Moll J, Pesenti E, Mercurio C, Ciomei M. Dual targeting of CDK and tropomyosin rec [Content Brief]

[3]. Degrassi A, et al. Efficacy of PHA-848125, a cyclin-dependent kinase inhibitor, on the K-Ras(G12D)LA2 lung adenocarcinoma transgenic mouse model: evaluation by multimodality imaging. Mol Cancer Ther. 2010 Mar;9(3):673-81. [Content Brief]

[4]. Brasca, M.G., et al. Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J. Med. Chem. 52(16) [Content Brief]

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 Milciclib, 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 Milciclib, whereas a further group receives two cycles of Milciclib 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	[1]. Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, Del Bufalo D, Desideri M, Bonmassar E, Pfeffer U, D'Atri S. Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhib [Content Brief] [2]. Albanese C, Alzani R, Amboldi N, Avanzi N, Ballinari D, Brasca MG, Festuccia C, Fiorentini F, Locatelli G, Pastori W, Patton V, Roletto F, Colotta F, Galvani A, Isacchi A, Moll J, Pesenti E, Mercurio C, Ciomei M. Dual targeting of CDK and tropomyosin rec [Content Brief] [3]. Degrassi A, et al. Efficacy of PHA-848125, a cyclin-dependent kinase inhibitor, on the K-Ras(G12D)LA2 lung adenocarcinoma transgenic mouse model: evaluation by multimodality imaging. Mol Cancer Ther. 2010 Mar;9(3):673-81. [Content Brief] [4]. Brasca, M.G., et al. Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J. Med. Chem. 52(16) [Content Brief]

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Keywords:

Milciclib802539-81-7PHA-848125PHA848125PHA 848125CDKAutophagyCyclin dependent kinaseInhibitorinhibitorinhibit

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Milciclib (Synonyms: PHA-848125)

Customer Review

5 Publications Citing Use of MCE Milciclib

Featured Recommendations

•Related Screening Libraries:

View All CDK Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

Molarity Calculator

Dilution Calculator

The molarity calculator equation

The dilution calculator equation

Keywords:

Your Recently Viewed Products:

Customer Review

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