2. PI3K/Akt/mTOR
  3. PI3K
  4. NVP-CLR457

NVP-CLR457 (compound 40) is an orally active, potent and balanced pan-class I PI3K inhibitor. NVP-CLR457 shows a clear dose-dependent PK/PD/efficacy relationship. NVP-CLR457 has antitumor activity.

For research use only. We do not sell to patients.

NVP-CLR457 Chemical Structure

NVP-CLR457 Chemical Structure

CAS No. : 1453082-52-4

Size Stock
50 mg   Get quote  
100 mg   Get quote  
250 mg   Get quote  
Synthetic products have potential research and development risk.

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

NVP-CLR457 Related Antibodies

Top Publications Citing Use of Products

View All PI3K Isoform Specific Products:

View All Isoforms
PI3Kα PI3Kβ PI3Kγ PI3Kδ PI3KC2α PI3KC2β PI3KC2γ Vps34 PI3K PI3KC3 p120γ

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

NVP-CLR457 (compound 40) is an orally active, potent and balanced pan-class I PI3K inhibitor. NVP-CLR457 shows a clear dose-dependent PK/PD/efficacy relationship. NVP-CLR457 has antitumor activity[1].

IC50 & Target

PI3Kα

12 ± 1.5 nM (IC50)

PI3Kβ

8.3 ± 1.0 nM (IC50)

PI3Kδ

8.3 ± 2.0 nM (IC50)

PI3Kγ

230 ± 31 nM (IC50)

In Vitro

NVP-CLR457 (compound 40) shows the mTOR activity, with an IC50 of 2474 ± 722 nM, and inhibits RPS6 phosphorylation with an IC50 of 1633 ± 54 nM[1].
NVP-CLR457 has no impact on the DDR response at concentrations of 1 and 5 μM[1].
NVP-CLR457 has no effect on the rate of microtubule polymerization[1].

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

NVP-CLR457 Related Antibodies

Western Blot Analysis

Cell Line: U87MG cells[1]
Concentration: 0, 1. 4, 16, 63, 250, 1000 nM
Incubation Time: 24 h
Result: Inhibited the readouts of class I PI3K activity in a dose-dependent manner, with IC50 and IC90 values of 100 and 507 nM determined for the inhibition of S473P-Akt, and had no significant change in the readouts of mTOR activity.
In Vivo

NVP-CLR457 (compound 40) (athymic nude mice bearing xenotransplanted Rat1-myr-p110α tumors, 3-20 mg/kg, PO, daily for 8 days) shows a dose-dependent inhibition of tumor growth[1].
NVP-CLR457 (Mice bearing xenograft HBRX2524 human primary breast tumor, 40 mg/kg, PO, daily for 15 days) inhibits the tumor growth throughout the study[1].
NVP-CLR457 (male Sprague-Dawley rats, 1.0 mg/kg, IV; 3.0 mg/kg, PO; once) shows high level of oral exposure and bioavailability[1].
Pharmacokinetic Parameters of NVP-CLR457 in male Sprague-Dawley rats[1].

compound 40
CL (mL/min/kg) 22 ± 6
Vss (L/kg) 4.4 ± 0.2
t1/2 (h) 3.3 ± 0.2
AUC iv (nM*h) 1770 ± 443
oral F (%) 97 ± 20
HDM FA (%) 37
NVP-CLR457 (3 mg/kg (IV) and 10 mg/kg (PO) for female OF1 mice, 0.1 mg/kg (IV), 0.3 mg/kg (PO) for male beagle dogs, once) shows low clearance, moderate volume of distribution, and rapid absorption leading to moderate to long half-lives and high oral bioavailability[1].
Pharmacokinetic Parameters of NVP-CLR457 in female OF1 mice and male beagle dogs[1].
species mouse dog
PPB (%) 76 71
CL (mL/min/kg) 10 3 ± 0
Vss (L/kg) 2 1.5 ± 0.2
t1/2 (h) 2 11 ± 3
AUC iv (nM*h) 3580 11213 ± 1169
AUC po (nM*h) 1738 11034 ± 1531
oral F (%) 49 98 ± 14
Cmax (nM) 422 1121 ± 128
Tmax (h) 0.5 1.3 ± 0.6
NVP-CLR457 (0.3-100 mg/kg, PO, once) leads to under-proportional increases in exposure (both AUC and Cmax) and much longer Tmax values[1].
Pharmacokinetic Parameters of NVP-CLR457 in male Sprague Dawley rats, male beagle dogs[1].
species rat dog
dose (mg/kg) 3 30 100 0.3 3
AUC (nM*h) 1709 ± 362 913 ± 251 784 ± 342 12,970 ± 1828 11,213 ± 1169
Cmax (nM) 213 ± 61 41 ± 6 22 ± 4 1121 ± 128 309 ± 40
Tmax (h) 0.5-2 4–24 24 1-2 2-24

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

Animal Model: Sprague Dawley rats (male)[1]
Dosage: 1 mg/kg (IV), 3 mg/kg (PO)
Administration: IV or PO, once (Pharmacokinetic Analysis)
Result: Showed high level of oral exposure and bioavailability.
Animal Model: Female OF1 mice, male beagle dogs[1]
Dosage: 3 mg/kg (IV) and 10 mg/kg (PO) for mice, 0.1 mg/kg (IV), 0.3 mg/kg (PO) for dogs
Administration: IV or PO, once (Pharmacokinetic Analysis)
Result: Showed low clearance, moderate volume of distribution, and rapid absorption leading to moderate to long half-lives and high oral bioavailability.
Animal Model: Male Sprague Dawley rats, male beagle dogs[1]
Dosage: 0.3, 3, 30, 100 mg/kg
Administration: PO, once (Pharmacokinetic Analysis)
Result: Led to under-proportional increases in exposure (both AUC and Cmax) and much longer Tmax values when it formulated as a suspension of the crystalline material.
Animal Model: Female athymic nude mice (bearing xenotransplanted Rat1-myr-p110α tumors)[1]
Dosage: 3, 10, and 20 mg/kg
Administration: PO, daily for 8 days
Result: Observed dose-dependent exposure and PD responses, and showed a dose-dependent inhibition of tumor growth. The 3 mg/kg dose achieved 80% S473P-Akt inhibition only at the 1 h time point; the 10 mg/kg dose at the 1 and 4 h time points; and the 20 mg/kg at the 1, 4, and 10 h time points, with a high level of inhibition remaining at the 14 h time point (76%).
Animal Model: Mice bearing xenograft HBRX2524 human primary breast tumor[1] Dosage: 40 mg/kg
Dosage: 40 mg/kg
Administration: PO, daily for 15 days
Result: Inhibited the tumor growth throughout the study, and showed a significant level of regression the end of the 15 day treatment period.
Molecular Weight

455.39

Formula

C18H20F3N7O4
CAS No.
SMILES

NC1=NC(C(F)(F)F)=C(C2=NC(N3CCOCC3)=NC(N4[C@H]([C@H](OC4=O)C)CO)=C2)C=N1
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.

NVP-CLR457 Related Classifications

  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2
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.

Keywords:

NVP-CLR4571453082-52-4PI3KPhosphoinositide 3-kinaseU87MG cellsHematological cell linesRat1-myr-p110α tumorsHBRX2524 human primary breast tumorOrally activeAntitumor activityInhibitorinhibitorinhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

  

Salutation

Applicant Name *

 

Email Address *

Phone Number *

 

Organization Name *

Department *

 

Requested quantity *

Country or Region *

      

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
NVP-CLR457
Cat. No.:
HY-146260
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email Address *

Phone Number

 

Department *

Organization Name *

 

Country or Region *

Remarks

Request for HNMR Report

We have received your request and will respond to you as soon as possible.