Cat. No.: HY-12296

Navtemadlin

(Synonyms: AMG 232; KRT-232)

26 Cited Publications

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Based on 26 publication(s) in Google Scholar

Navtemadlin (AMG 232) is a potent, selective and orally available inhibitor of p53-MDM2 interaction, with an IC₅₀ of 0.6 nM. Navtemadlin binds to MDM2 with a K_d of 0.045 nM.

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Pureté: 99.17%
CAS No.: 1352066-68-2
Formule: C₂₈H₃₅Cl₂NO₅S
Masse moléculaire:568.55

Stockage:

Powder -20°C, 3 years , 4°C, 2 years

* The compound is unstable in solutions, freshly prepared is recommended.

Navtemadlin Chemical Structure

CAS No.: 1352066-68-2

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Activité biologique
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Essai clinique
Chemical Information
Publications (26)
Solvant et solubilité
- In Vitro
- In Vivo
Pureté et documentation
Références
Help & FAQs
Classifications
Bioz

Activité biologique

Description

Navtemadlin (AMG 232) is a potent, selective and orally available inhibitor of p53-MDM2 interaction, with an IC₅₀ of 0.6 nM. Navtemadlin binds to MDM2 with a K_d of 0.045 nM^[1]^[2].

IC₅₀ & Target

IC50: 0.6 nM (p53-MDM2 interaction)^[1]
Kd: 0.045 nM (MDM2)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
A-375	IC₅₀	0.6 μM Compound: AMG-232	Antiproliferative activity against human A-375 cells assessed as inhibition of cell growth incubated for 72 hrs by WST assay Antiproliferative activity against human A-375 cells assessed as inhibition of cell growth incubated for 72 hrs by WST assay	[PMID: 37130471]
CWR22R	IC₅₀	0.3 μM Compound: AMG-232	Antiproliferative activity against human 22Rv1 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay Antiproliferative activity against human 22Rv1 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay	[PMID: 37130471]
HCT-116	GI₅₀	33 μM Compound: AMG 232	Antiproliferative activity against human HCT116 p53-/- cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis Antiproliferative activity against human HCT116 p53-/- cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis	[PMID: 29691156]
HCT-116	GI₅₀	7 μM Compound: AMG 232	Antiproliferative activity against human HCT116 p53+/+ cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis Antiproliferative activity against human HCT116 p53+/+ cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis	[PMID: 29691156]
HCT-116	IC₅₀	>25 μM Compound: 2, AMG 232	Antiproliferative activity against p53 -deficient human HCT116 cells after 16 hrs by BrdU proliferation assay Antiproliferative activity against p53 -deficient human HCT116 cells after 16 hrs by BrdU proliferation assay	[PMID: 24456472]
HCT-116	IC₅₀	10 nM Compound: 2, AMG 232	Antiproliferative activity against human HCT116 cells expressing p53 wild type after 16 hrs by BrdU proliferation assay Antiproliferative activity against human HCT116 cells expressing p53 wild type after 16 hrs by BrdU proliferation assay	[PMID: 24456472]
Hepatocyte	IC₅₀	6.3 nM Compound: 1, AMG 232	Intrinsic clearance in human hepatocytes measured per million cells Intrinsic clearance in human hepatocytes measured per million cells	[PMID: 25384157]
MDA-MB-231	IC₅₀	>10 μM Compound: AMG-232	Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay	[PMID: 37130471]
SJSA-1	ED₅₀	2.8 nM Compound: 2, AMG 232	Antiproliferative activity against human SJSA1 cells xenografted in athymic nude mouse assessed as unbound concentration causing inhibition of tumor growth treated after 11 days of tumor xenograft upto 25 days through oral gavage relative to vehicle treat Antiproliferative activity against human SJSA1 cells xenografted in athymic nude mouse assessed as unbound concentration causing inhibition of tumor growth treated after 11 days of tumor xenograft upto 25 days through oral gavage relative to vehicle treat	[PMID: 24456472]
SJSA-1	ED₅₀	9.1 mg/kg Compound: 2, AMG 232	Antiproliferative activity against human SJSA1 cells xenografted in athymic nude mouse assessed as inhibition of tumor growth treated after 11 days of tumor xenograft upto 25 days through oral gavage relative to vehicle treated control Antiproliferative activity against human SJSA1 cells xenografted in athymic nude mouse assessed as inhibition of tumor growth treated after 11 days of tumor xenograft upto 25 days through oral gavage relative to vehicle treated control	[PMID: 24456472]
SJSA-1	ED₅₀	9.1 mg/kg Compound: 13	Antitumor activity against human SJSA1 cells xenografted in athymic nude mouse administered once via oral gavage Antitumor activity against human SJSA1 cells xenografted in athymic nude mouse administered once via oral gavage	[PMID: 30253242]
SJSA-1	IC₅₀	25 nM Compound: 39; AMG232	Antiproliferative activity against human SJSA-1 cells Antiproliferative activity against human SJSA-1 cells	[PMID: 33423841]
SJSA-1	IC₅₀	47 nM Compound: 1, AMG 232	Binding affinity to MDM2 in human SJSA1 cells assessed as induction of p21 gene level after 7 hrs by qRT-PCR assay in presence of 10% human serum Binding affinity to MDM2 in human SJSA1 cells assessed as induction of p21 gene level after 7 hrs by qRT-PCR assay in presence of 10% human serum	[PMID: 25384157]
SJSA-1	IC₅₀	9.1 nM Compound: 2, AMG 232	Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 1 hr by Click-iT EdU HCS assay in presence of 10% human serum Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 1 hr by Click-iT EdU HCS assay in presence of 10% human serum	[PMID: 24456472]
SJSA-1	IC₅₀	9.2 nM Compound: 1, AMG 232	Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 16 hrs by Click-iT EdU HCS assay in presence of 10% human serum Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 16 hrs by Click-iT EdU HCS assay in presence of 10% human serum	[PMID: 25384157]

In Vitro

Navtemadlin (AMG 232) (10 μM) induces p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines^[1].
Navtemadlin potently inhibits proliferation of non-MDM2-amplified HCT116 colorectal cells (IC₅₀=10 nM)^[3].

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

Cell Viability Assay^[1]

Cell Line:

SJSA-1, HCT116, ACHN, NCI-H460, MOLM-13, RKO, MCF7, 22RV1, HT-29, PC-3, NCI-H82, NCI-SNU1, MG-63, NCI-H2452, SW982, C32, SK-HEP-1, A375, RT4, RPMI2650, MDA-MB-134-VI, NCI-H2347 and A427 cells.
Concentration:

0-10 μM.
Incubation Time:

72 hours.
Result:

Induced p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines (SJSA-1, HCT116, and ACHN).
Caused robust p21 mRNA induction between 9.76 and 34.9 fold with IC50 values ranging from 12.8 to 46.8 nM.

In Vivo

Navtemadlin (AMG 232) (10, 25, 75 mg/kg, once daily, p.o.) activates p53 pathway activity in vivo^[1].
Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) potently inhibits growth of tumor xenografts in mice^[1].
Navtemadlin (10, 25, 75 mg/kg, once daily, p.o.) blocks DNA synthesis and induces apoptosis in vivo^[1].
Navtemadlin causes a dose-dependent tumor growth inhibition with an ED₅₀ of 16 mg/kg^[2].

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

Animal Model:

Female athymic nude mice (n=10/group) based cancer models^[1].
Dosage:

10, 25, 75 mg/kg.
Administration:

Once daily by oral gavage.
Result:

Resulted in significant tumor growth inhibition across all models. SJSA-1, an MDM2 amplified osteosarcoma model, was the most sensitive to AMG 232 treatment with an ED₅₀ of 9.1 mg/kg. In the highest dose group of 75 mg/kg, 10/10 tumors completely regressed and were undetectable after 10 days of treatment.

Essai clinique

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 1352066-68-2
Appearance Solid
Masse moléculaire 568.55
Formule C₂₈H₃₅Cl₂NO₅S
Color White to light yellow
SMILES

O=C(O)C[C@]1(C)C(N([C@H](CS(=O)(C(C)C)=O)C(C)C)[C@H](C2=CC=C(Cl)C=C2)[C@@H](C3=CC=CC(Cl)=C3)C1)=O
Synonyms

AMG 232; KRT-232
Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years

* The compound is unstable in solutions, freshly prepared is recommended.

Publications (26)

All WBCell Proliferation/Viability AssayFlow CytometryIHC

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Journal Impact Factor

Nat Genet

Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations. [Abstract]

2025 Jan;57(1):140-153. PMID: 39774325
Cancer Res

Chemoradiation Reprograms Tumor Cells and the Immune Microenvironment in Cervical Cancer. [Abstract]

2026 Mar 20:OF1-OF18. PMID: 41860764
Sci Transl Med

A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma. [Abstract]

2025 Feb 19;17(786):eadn6274. PMID: 39970230

Navtemadlin purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Feb 19;17(786):eadn6274. [Abstract]

Immunoblotting of BT145 and BT286 cells treated with Navtemadlin (50 nM; 3-48 h) over time.

Navtemadlin purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Feb 19;17(786):eadn6274. [Abstract]

Dose response curves showed the sensitivity of TP53 wild-type GBM cells (BT145 and BT286; yellow), TP53 mutant GBM cells (BT359; red), bone marrow cells (BMMC; gray), human immortalized astrocytes (hAstro; dark gray), and human neural stem cells (hNSC; light gray) to Navtemadlin (1-10000 nM).

Navtemadlin purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Feb 19;17(786):eadn6274. [Abstract]

Immunoblotting of BT145 and BT286 cells treated with increasing concentrations of Navtemadlin (10-1000 nM; 72 h).

Navtemadlin purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Feb 19;17(786):eadn6274. [Abstract]

Effect of increased Navtemadlin (10-1000 nM; 72 h) treatment on death of BT145 and BT286 cells.

Navtemadlin purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2025 Feb 19;17(786):eadn6274. [Abstract]

Navtemadlin (120-240 mg; p.o.; 2 d) significantly increased the percentage of tumor cells expressing CDKN1A and decreased the proliferative marker Ki67 in recurrent TP53 wild-type glioblastoma.
Cell Death Discov

CeDaD-a novel assay for simultaneous tracking of cell death and division in a single population. [Abstract]

2025 Mar 4;11(1):86. PMID: 40038265
Cell Death Discov

AMG-232 sensitizes high MDM2-expressing tumor cells to T-cell-mediated killing. [Abstract]

2020 Jul 6;6:57. PMID: 32655895

Navtemadlin purchased from MedChemExpress. Usage Cited in: Cell Death Discov. 2020 Jul 6;6:57. [Abstract]

The effect of AMG-232 on the p53 signaling pathway, and the expression of IL-6 and PD-L1 at different drug doses is assessed by immunoblotting. AMG-232 treatment leads to activation of the p53 signaling pathway in the cancer cells in a dose-dependent manner. The effect of significant reduction in IL-6 expression is observed with AMG-232 in a dose-dependent manner.
Clin Transl Med

Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology. [Abstract]

2022 Jul;12(7):e961. PMID: 35839307
Br J Cancer

Functional genomics of human clear cell sarcoma: genomic, transcriptomic and chemical biology landscape for clear cell sarcoma. [Abstract]

2023 May;128(10):1941-1954. PMID: 36959380
Cells

PROTAC-Mediated Targeted Degradation of MDM2 Induces Tumor-Suppressive Signaling in Osteosarcoma Cells. [Abstract]

2026 Mar 5;15(5):473. PMID: 41827906
BMC Biol

A yeast two-hybrid system for the screening and characterization of small-molecule inhibitors of protein-protein interactions identifies a novel putative Mdm2-binding site in p53. [Abstract]

2017 Nov 9;15(1):108. PMID: 29121928
Med Oncol

Evaluation of the antiangiogenic effect of AMG232 in multiple myeloma coculture systems. [Abstract]

2025 Mar 13;42(4):107. PMID: 40082344
JCO Precis Oncol

Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers and MDM2 Amplification. [Abstract]

2024 Sep:8:e2400241. PMID: 39259915
iScience

MDM2/MDMX inhibition by Sulanemadlin synergizes with anti-Programmed Death 1 immunotherapy in wild-type p53 tumors. [Abstract]

2024 May 6;27(6):109862. PMID: 38784022
Biomedicines

High-Throughput Drug Library Screening in Primary KMT2A-Rearranged Infant ALL Cells Favors the Identification of Drug Candidates That Activate P53 Signaling. [Abstract]

2022 Mar 10;10(3):638. PMID: 35327440
J Cell Sci

AMG232 inhibits the angiogenesis in glioma through p53/RBM4/VEGFR2 pathway. [Abstract]

2023 Jan 15;136(2):jcs260270. PMID: 36601864
Exp Dermatol

Enhanced expression of p21 promotes sensitivity of melanoma cells towards targeted therapies. [Abstract]

2022 Aug;31(8):1243-1252. PMID: 35514255
Biomed Chromatogr

Quantitation of navtemadlin in human plasma and brain tissue by liquid chromatography-tandem mass spectrometry. [Abstract]

2022 Jul 27;e5467. PMID: 35895384
Rep Biochem Mol Biol

AMG-232, a New Inhibitor of MDM-2, Enhance Doxorubicin Efficiency in Pre-B Acute Lymphoblastic Leukemia Cells. [Abstract]

2022 Apr;11(1):111-124. PMID: 35765530
bioRxiv

2026 Mar 30.
bioRxiv

TET2 and TP53 Mutations Cooperatively Modulate the Response to Inflammation to Promote Leukemic Transformation. [Abstract]

2026 Jan 20:2026.01.20.700390. PMID: 41648254
University of Wisconsin

2025.
medRxiv

Surgical window of opportunity trial reveals mechanisms of response and resistance to navtemadlin (KRT-232) in patients with recurrent glioblastoma. [Abstract]

2024 Aug 14:2024.08.12.24311893. PMID: 39211865
University of Gothenburg

2023 Jun 27.
bioRxiv

2023 Mar 10.
Patent

US20210379039A1.
bioRxiv

2021 Dec.
Evid Based Complement Alternat Med

Berbamine Inhibits Cell Proliferation and Migration and Induces Cell Death of Lung Cancer Cells via Regulating c-Maf, PI3K/Akt, and MDM2-P53 Pathways. [Abstract]

2021 Jul 8:2021:5517143. PMID: 34306137

Solvant et solubilité

In Vitro:

DMSO : ≥ 50 mg/mL (87.94 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

* "≥" means soluble, but saturation unknown.

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.7589 mL

8.7943 mL

17.5886 mL

5 mM

0.3518 mL

1.7589 mL

3.5177 mL

10 mM

0.1759 mL

0.8794 mL

1.7589 mL

Please refer to the solubility information to select the appropriate solvent. The compound is unstable in solutions, freshly prepared is recommended.

Calculateur de molarité

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculateur de dilution

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

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

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

Stock Solution Working Solution

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 (4.40 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.

Protocol 2

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

Solubility: ≥ 2.5 mg/mL (4.40 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.

Protocol 3

Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline

Solubility: ≥ 2.5 mg/mL (4.40 mM); Clear solution

Working Solution

For the following dissolution methods, please prepare the working solution directly:

It is recommended to prepare fresh solutions and use them promptly within a short period of time.

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: PBS

Solubility: 1.5 mg/mL (2.64 mM); Clear solution; Need ultrasonic

Protocol 2

Add each solvent one by one: 50% PEG300 50% Saline

Solubility: 10 mg/mL (17.59 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

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).

Working solution concentration: 0.22 mg/mL

Pureté et documentation

Select Batch:

Pureté: 99.98%

Assay: 99.98%

ee.: 99.98%

Fiche technique (284 KB)
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COA (2659 KB)
Elemental Analysis Report (2659 KB)
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Références

[1]. Canon J, et al. The MDM2 Inhibitor AMG 232 Demonstrates Robust Antitumor Efficacy and Potentiates the Activity of p53-Inducing Cytotoxic Agents. Mol Cancer Ther. 2015 Mar;14(3):649-58. [Content Brief]

[2]. Rew Y, et al. Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer. J Med Chem. 2014 Aug 14;57(15):6332-41. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Please refer to the solubility information to select the appropriate solvent. The compound is unstable in solutions, freshly prepared is recommended.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.7589 mL	8.7943 mL	17.5886 mL	43.9715 mL
	5 mM	0.3518 mL	1.7589 mL	3.5177 mL	8.7943 mL
	10 mM	0.1759 mL	0.8794 mL	1.7589 mL	4.3972 mL
	15 mM	0.1173 mL	0.5863 mL	1.1726 mL	2.9314 mL
	20 mM	0.0879 mL	0.4397 mL	0.8794 mL	2.1986 mL
	25 mM	0.0704 mL	0.3518 mL	0.7035 mL	1.7589 mL
	30 mM	0.0586 mL	0.2931 mL	0.5863 mL	1.4657 mL
	40 mM	0.0440 mL	0.2199 mL	0.4397 mL	1.0993 mL
	50 mM	0.0352 mL	0.1759 mL	0.3518 mL	0.8794 mL
	60 mM	0.0293 mL	0.1466 mL	0.2931 mL	0.7329 mL
	80 mM	0.0220 mL	0.1099 mL	0.2199 mL	0.5496 mL

Keywords

Navtemadlin

26 Cited Publications

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Navtemadlin

Peptidomimetic Library

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Publications Citing Use of MedChemExpress (MCE) Navtemadlin

Activité biologique

Chemical Information

Publications (26)

Solvant et solubilité

Pureté et documentation

Références

Help & FAQs

Complete Stock Solution Preparation Table

Navtemadlin

Peptidomimetic Library

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Publications Citing Use of MedChemExpress (MCE) Navtemadlin

Activité biologique

Chemical Information

Publications (26)

Solvant et solubilité

Pureté et documentation

Références

Help & FAQs

Complete Stock Solution Preparation Table

Navtemadlin Related Classifications

HY-12296 Related Classifications