2. Apoptosis Metabolic Enzyme/Protease
  3. MDM-2/p53 E1/E2/E3 Enzyme
  4. Siremadlin

Siremadlin  (Synonyms: NVP-HDM201; HDM201)

Cat. No.: HY-18658 Purity: 99.87% ee.: 97.51%
COA Handling Instructions

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Siremadlin (NVP-HDM201) is a potent, orally bioavailable and highly specific p53-MDM2 interaction inhibitor.

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

Siremadlin Chemical Structure

Siremadlin Chemical Structure

CAS No. : 1448867-41-1

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 202 In-stock
Solution
10 mM * 1 mL in DMSO USD 202 In-stock
Solid
1 mg USD 77 In-stock
5 mg USD 165 In-stock
10 mg USD 242 In-stock
50 mg USD 715 In-stock
100 mg USD 1210 In-stock
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 4 publication(s) in Google Scholar

Other Forms of Siremadlin:

Siremadlin Related Antibodies

Top Publications Citing Use of Products

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

Siremadlin (NVP-HDM201) is a potent, orally bioavailable and highly specific p53-MDM2 interaction inhibitor.

In Vitro

Siremadlin (NVP-HDM201) disrupts both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation[1].

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

Siremadlin Related Antibodies
In Vivo

Siremadlin (NVP-HDM201) is an imidazolopyrrolidinone analogue, showing a very advantageous in vivo profile. NVP-HDM201 has recently entered Phase 1 clinical trials in cancer patients[2]. Constitutive PB mutagenesis in Arf−/− mice provides a collection of spontaneous tumors with characterized insertional genetic landscapes. Tumors are allografted in large cohorts of mice to assess the pharmacologic effects of Siremadlin (NVP-HDM201). Sixteen out of 21 allograft models are sensitive to Siremadlin (NVP-HDM201) but ultimately relapse under treatment. A comparison of tumors with acquired resistance to Siremadlin (NVP-HDM201) and untreated tumors identified 87 genes that are differentially and significantly targeted by the PB transposon[1]. Siremadlin (NVP-HDM201) administered either daily at a low dose or once at a high dose revealed a differentiated engagement of the p53 molecular response. In contrast to the daily low dose treatment regimen, the single high dose Siremadlin (NVP-HDM201) regimen results in a rapid and dramatic induction of p53-dependent PUMA expression and apoptosis. This is consistent with the finding that a single high dose Siremadlin (NVP-HDM201) treatment, administered orally or intravenously, results in a robust and sustained tumor regression. Overall, both daily and once every 3 weeks dosing regimen shows comparable long term efficacy in preclinical studies. The ongoing clinical trial is currently designed to compare both dosing regimens with regard to efficacy and tolerability[3].

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

555.41

Formula

C26H24Cl2N6O4
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C1N(C2=CC(Cl)=CN(C)C2=O)[C@@H](C3=CC=C(Cl)C=C3)C4=C1N=C(C5=CN=C(OC)N=C5OC)N4C(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 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : ≥ 56.75 mg/mL (102.18 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.8005 mL 9.0024 mL 18.0047 mL
5 mM 0.3601 mL 1.8005 mL 3.6009 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
=
Concentration
×
Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (4.50 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (4.50 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.87% ee.: 97.51%

COA (256 KB) HNMR (257 KB) NP-HPLC (177 KB) LCMS (97 KB)

Handling Instructions (2659 KB)
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.8005 mL 9.0024 mL 18.0047 mL 45.0118 mL
5 mM 0.3601 mL 1.8005 mL 3.6009 mL 9.0024 mL
10 mM 0.1800 mL 0.9002 mL 1.8005 mL 4.5012 mL
15 mM 0.1200 mL 0.6002 mL 1.2003 mL 3.0008 mL
20 mM 0.0900 mL 0.4501 mL 0.9002 mL 2.2506 mL
25 mM 0.0720 mL 0.3601 mL 0.7202 mL 1.8005 mL
30 mM 0.0600 mL 0.3001 mL 0.6002 mL 1.5004 mL
40 mM 0.0450 mL 0.2251 mL 0.4501 mL 1.1253 mL
50 mM 0.0360 mL 0.1800 mL 0.3601 mL 0.9002 mL
60 mM 0.0300 mL 0.1500 mL 0.3001 mL 0.7502 mL
80 mM 0.0225 mL 0.1125 mL 0.2251 mL 0.5626 mL
100 mM 0.0180 mL 0.0900 mL 0.1800 mL 0.4501 mL
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Siremadlin Related Classifications

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:

Siremadlin1448867-41-1NVP-HDM201 HDM201HDM201HDM 201HDM-201MDM-2/p53E1/E2/E3 EnzymeE1 activating enzymeE2 conjugating enzymeE3 ligating enzymeUbiquitin activating enzymeUbiquitin conjugating enzymeUbiquitin ligaseInhibitorinhibitorinhibit

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