Referencia número: HY-10943

GNF-7

2 Cited Publications

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Based on 2 publication(s) in Google Scholar

GNF-7 is a multikinase inhibitor. GNF-7 is a Bcr-Abl inhibitor, with IC₅₀s of 133 nM and 61 nM for Bcr-Abl^WT and Bcr-Abl^T315I, respectively. GNF-7 also possesses inhibitory activity against both ACK1 (activated CDC42 kinase 1) and GCK (germinal center kinase) with IC₅₀s of 25 nM and 8 nM, respectively. GNF-7 can be used for the research of hematologic malignancies.

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Pureza: 99.70%
No. CAS: 839706-07-9
Fòrmula: C₂₈H₂₄F₃N₇O₂
Peso molecular:547.53

Almacenamiento:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

GNF-7 Chemical Structure

No. CAS: 839706-07-9

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Actividad biológica
- Descripciòn
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (2)
Solvente y solubilidad
- In Vitro
- In Vivo
Pureza y Documentación
Referencias
Help & FAQs
Classifications
Bioz

Actividad biológica

Descripciòn

IC₅₀ & Target

IC50: 133 nM (Bcr-Abl^WT)^[1], 61 nM (Bcr-Abl^T315I)^[1], 25 nM (ACK1)^[3], 8 nM (GCK)^[3]

Ver todos los productos específicos de isoformas Bcr-Abl :

Abl
Bcr-Abl

Cellular Effect

Cell Line	Type	Value	Description	References
BaF3	GI₅₀	0.005 μM Compound: 27; GNF-7	Inhibition of Tel-ABL (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition after 72 hrs by CellTiter-Glo or CCK-8 assay Inhibition of Tel-ABL (unknown origin) expressed in mouse BA/F3 cells assessed as cell growth inhibition after 72 hrs by CellTiter-Glo or CCK-8 assay	[PMID: 26789553]
BaF3	GI₅₀	0.014 μM Compound: 27; GNF-7	Inhibition of BCR/ABL p210 (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo or CCK-8 assay Inhibition of BCR/ABL p210 (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by CellTiter-Glo or CCK-8 assay	[PMID: 26789553]
BaF3	GI₅₀	0.12 μM Compound: 27; GNF-7	Antiproliferative activity against mouse BA/F3 cells assessed as cell viability after 72 hrs by CellTiter-Glo or CCK-8 assay Antiproliferative activity against mouse BA/F3 cells assessed as cell viability after 72 hrs by CellTiter-Glo or CCK-8 assay	[PMID: 26789553]
BaF3	GI₅₀	0.12 μM Compound: 6; GNF-7	Growth inhibition of mouse BAF3 cells after 72 hrs by CellTiter-Glo or CCK-8 assay Growth inhibition of mouse BAF3 cells after 72 hrs by CellTiter-Glo or CCK-8 assay	[PMID: 28140585]
BaF3	GI₅₀	1.033 μM Compound: GNF-7	Growth inhibition of parental mouse BA/F3 cells after 72 hrs by celltiter-glo assay Growth inhibition of parental mouse BA/F3 cells after 72 hrs by celltiter-glo assay	[PMID: 30153003]
BaF3	IC₅₀	<5 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl E255K mutant Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl E255K mutant	[PMID: 20604564]
BaF3	IC₅₀	<5 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl E255V mutant Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl E255V mutant	[PMID: 20604564]
BaF3	IC₅₀	<5 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl F317L mutant Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl F317L mutant	[PMID: 20604564]
BaF3	IC₅₀	<5 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl G250E mutant Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl G250E mutant	[PMID: 20604564]
BaF3	IC₅₀	<5 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl M351T mutant Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl M351T mutant	[PMID: 20604564]
BaF3	IC₅₀	<5 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl Q252H mutant Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl Q252H mutant	[PMID: 20604564]
BaF3	IC₅₀	<5 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl Y253H mutant Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl Y253H mutant	[PMID: 20604564]
BaF3	IC₅₀	<5 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing wild type Bcr-Abl Antiproliferative activity against mouse BA/F3 cells expressing wild type Bcr-Abl	[PMID: 20604564]
BaF3	IC₅₀	0.008 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing TrkC Antiproliferative activity against mouse BA/F3 cells expressing TrkC	[PMID: 20604564]
BaF3	IC₅₀	0.009 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing FGFR3 Antiproliferative activity against mouse BA/F3 cells expressing FGFR3	[PMID: 20604564]
BaF3	IC₅₀	0.011 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing PDGFR Antiproliferative activity against mouse BA/F3 cells expressing PDGFR	[PMID: 20604564]
BaF3	IC₅₀	0.012 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Flt3-ITD Antiproliferative activity against mouse BA/F3 cells expressing Flt3-ITD	[PMID: 20604564]
BaF3	IC₅₀	0.044 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing JAK1 Antiproliferative activity against mouse BA/F3 cells expressing JAK1	[PMID: 20604564]
BaF3	IC₅₀	0.05 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing JAK2 V617F mutant Antiproliferative activity against mouse BA/F3 cells expressing JAK2 V617F mutant	[PMID: 20604564]
BaF3	IC₅₀	0.127 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing JAK2 Antiproliferative activity against mouse BA/F3 cells expressing JAK2	[PMID: 20604564]
BaF3	IC₅₀	0.359 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Flt3 Antiproliferative activity against mouse BA/F3 cells expressing Flt3	[PMID: 20604564]
BaF3	IC₅₀	1.466 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing NPM-ALK Antiproliferative activity against mouse BA/F3 cells expressing NPM-ALK	[PMID: 20604564]
BaF3	IC₅₀	11 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl T315I mutant Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl T315I mutant	[PMID: 20604564]
BaF3	IC₅₀	1370 nM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells Antiproliferative activity against mouse BA/F3 cells	[PMID: 20604564]
BaF3	IC₅₀	2.018 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing JAK3 Antiproliferative activity against mouse BA/F3 cells expressing JAK3	[PMID: 20604564]
BaF3	IC₅₀	3.15 nM Compound: 4, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing wild type Bcr-Abl after 72 hrs by CCK-8 assay Antiproliferative activity against mouse BA/F3 cells expressing wild type Bcr-Abl after 72 hrs by CCK-8 assay	[PMID: 23088644]
BaF3	IC₅₀	3.401 μM Compound: 2, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing TPR-Met Antiproliferative activity against mouse BA/F3 cells expressing TPR-Met	[PMID: 20604564]
BaF3	IC₅₀	6.18 nM Compound: 4, GNF-7	Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl T315I mutant after 72 hrs by CCK-8 assay Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl T315I mutant after 72 hrs by CCK-8 assay	[PMID: 23088644]
COLO 205	IC₅₀	0.005 μM Compound: 2, GNF-7	Antiproliferative activity against human COLO205 cells Antiproliferative activity against human COLO205 cells	[PMID: 20604564]
HEK-293T	IC₅₀	>10 μM Compound: 2, GNF-7	Antiproliferative activity against human HEK293T cells Antiproliferative activity against human HEK293T cells	[PMID: 20604564]
HT-29	EC₅₀	100 nM Compound: GNF-7; 9	Anti-necroptic activity in TSZ induced necroptosis in human HT-29 cells pretreated with compound followed by TSZ stimulation for 8 hrs by celltiter-glo luminescent cell viability assay Anti-necroptic activity in TSZ induced necroptosis in human HT-29 cells pretreated with compound followed by TSZ stimulation for 8 hrs by celltiter-glo luminescent cell viability assay	[PMID: 36346971]
HT-29	EC₅₀	100 nM Compound: GNF-7; L4	Anti-necroptosis activity against TSZ-induced human HT-29 cells Anti-necroptosis activity against TSZ-induced human HT-29 cells	[PMID: 38199165]
K562	GI₅₀	0.009 μM Compound: 27; GNF-7	Antiproliferative activity against human K562 cells assessed as cell viability after 72 hrs by CellTiter-Glo or CCK-8 assay Antiproliferative activity against human K562 cells assessed as cell viability after 72 hrs by CellTiter-Glo or CCK-8 assay	[PMID: 26789553]
K562	IC₅₀	0.44 nM Compound: 4, GNF-7	Antiproliferative activity against human K562 cells expressing wild type Bcr-Abl after 72 hrs by CCK-8 assay Antiproliferative activity against human K562 cells expressing wild type Bcr-Abl after 72 hrs by CCK-8 assay	[PMID: 23088644]
K562	IC₅₀	2.6 nM Compound: 4, GNF-7	Antiproliferative activity against imatinib-resistant human K562 cells expressing Bcr-Abl Q252H mutant after 72 hrs by CCK-8 assay Antiproliferative activity against imatinib-resistant human K562 cells expressing Bcr-Abl Q252H mutant after 72 hrs by CCK-8 assay	[PMID: 23088644]
KU812 cell line	IC₅₀	0.08 nM Compound: 4, GNF-7	Antiproliferative activity against human KU812 cells expressing wild type Bcr-Abl after 72 hrs by CCK-8 assay Antiproliferative activity against human KU812 cells expressing wild type Bcr-Abl after 72 hrs by CCK-8 assay	[PMID: 23088644]
OCI-AML-3	GI₅₀	0.219 μM Compound: GNF-7	Growth inhibition of human OCI-AML3 cells harboring NRAS-Q61L mutant after 72 hrs by celltiter-glo assay Growth inhibition of human OCI-AML3 cells harboring NRAS-Q61L mutant after 72 hrs by celltiter-glo assay	[PMID: 30153003]
SW-620	IC₅₀	0.001 μM Compound: 2, GNF-7	Antiproliferative activity against human SW620 cells Antiproliferative activity against human SW620 cells	[PMID: 20604564]
U-87MG ATCC	IC₅₀	5.956 μM Compound: 2, GNF-7	Antiproliferative activity against human U87 cells Antiproliferative activity against human U87 cells	[PMID: 20604564]
U-937	GI₅₀	4.377 μM Compound: GNF-7	Growth inhibition of parental human U937 cells after 72 hrs by celltiter-glo assay Growth inhibition of parental human U937 cells after 72 hrs by celltiter-glo assay	[PMID: 30153003]

In Vitro

GNF-7 potently inhibits wild-type Bcr-Abl (IC₅₀<5 nM) and Bcr-Abl mutants such as T315I (IC₅₀=11 nM), G250E (IC₅₀<5 nM), E255V (IC₅₀=10 nM), F317L (IC₅₀<5 nM) and M351T (IC₅₀<5 nM) in cellular assays^[2].
GNF-7 (1 μM; 2 hours) suppresses AKT/mTOR signaling and GCK downstream^[3].
GNF-7 (1 μM; 24 hours) induces of apoptosis and cell cycle arrest in NRAS mutant cell lines^[3].

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

Western Blot Analysis^[3]

Cell Line:

Ba/F3-NRAS-G12D cells, OCI-AML3 cells
Concentration:

1 μM
Incubation Time:

2 hours
Result:

Caused a decreased level of phosphorylation of p70S6K1, AKT (S473), JNK, and p38.

Apoptosis Analysis^[3]

Cell Line:

OCI-AML3 cells
Concentration:

1 μM
Incubation Time:

24 hours
Result:

Increased the levels of both cleaved PARP and cleaved caspase 3 and diminished bcl-2 and MCL1.

Cell Cycle Analysis^[3]

Cell Line:

OCI-AML3 cells
Concentration:

1 μM
Incubation Time:

24 hours
Result:

Induced of G0-G1 arrest.

In Vivo

GNF-7 (10-20 mg/kg; o.p.; daily; for 7 days) displays significant in vivo efficacy against T315I Bcr-Abl in the bioluminescent xenograft mouse model^[2].
GNF-7 exhibits moderate oral bioavailability (mice 36%) and C_max (mice 3616 nM) following oral administration (mice 20 mg/kg)^[2].
GNF-7 exhibits terminal elimination half-lives (mice 3.8 h) due to high plasma clearance (8.6 mL/min/kg) following intravenous injection (mice 5 mg/kg)^[2].

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

Animal Model:

6-8 weeks old SCID beige female mice, with Ba/F3-T315I-Bcr-Abl cells xenograft^[2]
Dosage:

10 mg/kg, 20 mg/kg
Administration:

Oral administration, daily, for 7 days
Result:

Effectively inhibited tumor growth of T315I-Bcr-Abl-Ba/F3 cells in mice at low doses (10 mg/kg).

Animal Model:

5-6 weeks old male Balb/c mice (20-25 g)^[2]
Dosage:

5 mg/kg for i.v.; 20 mg/kg for i.g. (Pharmacokinetic Analysis)
Administration:

Intravenous injection and oral gavage
Result:

Oral bioavailability (36%), C_max (3616 nM), T_1/2 (3.2 h).

Chemical Information

No. CAS 839706-07-9
Appearance Solid
Peso molecular 547.53
Fòrmula C₂₈H₂₄F₃N₇O₂
Color White to off-white
SMILES

O=C(NC1=CC=C(C)C(N2CC3=CN=C(NC4=CC=C(C)N=C4)N=C3N(C)C2=O)=C1)C5=CC=CC(C(F)(F)F)=C5
Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (2)

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Biochem Pharmacol

The Bcr-Abl inhibitor GNF-7 inhibits necroptosis and ameliorates acute kidney injury by targeting RIPK1 and RIPK3 kinases. [Abstract]

2020 Jul;177:113947. PMID: 32247850
Arch Pharm (Weinheim)

Discovery of potent CSK inhibitors through integrated virtual screening and molecular dynamic simulation. [Abstract]

2024 Sep;357(9):e2400066. PMID: 38809025

Solvente y solubilidad

In Vitro:

DMSO : 20 mg/mL (36.53 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

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Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.8264 mL

9.1319 mL

18.2638 mL

5 mM

0.3653 mL

1.8264 mL

3.6528 mL

10 mM

0.1826 mL

0.9132 mL

1.8264 mL

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.

Calculadora de molaridad

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculadora de dilución

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

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

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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 mg/mL (3.65 mM); Clear solution

This protocol yields a clear solution of ≥ 2 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 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% (20% SBE-β-CD in Saline)

Solubility: ≥ 2 mg/mL (3.65 mM); Clear solution

This protocol yields a clear solution of ≥ 2 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

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

Solubility: ≥ 2 mg/mL (3.65 mM); Clear solution

This protocol yields a clear solution of ≥ 2 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 (20.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

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

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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

Pureza y Documentación

Select Batch:

Pureza: 99.98%

Assay: 99.98%

ee.: 99.98%

Ficha de datos (277 KB)
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COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
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OR (2659 KB)
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Referencias

[1]. Lu X, et al. Hybrid pyrimidine alkynyls inhibit the clinically resistance related Bcr-Abl(T315I) mutant. Bioorg Med Chem Lett. 2015 Sep 1;25(17):3458-63. [Content Brief]

[2]. Choi HG, et al. A type-II kinase inhibitor capable of inhibiting the T315I "gatekeeper" mutant of Bcr-Abl. J Med Chem. 2010 Aug 12;53(15):5439-48. [Content Brief]

[3]. Cho, H., et al. First SAR study for overriding NRAS mutant driven acute myeloid leukemia. Journal of Medicinal Chemistry. [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

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	1.8264 mL	9.1319 mL	18.2638 mL	45.6596 mL
	5 mM	0.3653 mL	1.8264 mL	3.6528 mL	9.1319 mL
	10 mM	0.1826 mL	0.9132 mL	1.8264 mL	4.5660 mL
	15 mM	0.1218 mL	0.6088 mL	1.2176 mL	3.0440 mL
	20 mM	0.0913 mL	0.4566 mL	0.9132 mL	2.2830 mL
	25 mM	0.0731 mL	0.3653 mL	0.7306 mL	1.8264 mL
	30 mM	0.0609 mL	0.3044 mL	0.6088 mL	1.5220 mL

Keywords

GNF-7

2 Cited Publications

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GNF-7

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Ver todos los productos específicos de isoformas Bcr-Abl

Actividad biológica

Chemical Information

Publications (2)

Solvente y solubilidad

Pureza y Documentación

Referencias

Help & FAQs

Complete Stock Solution Preparation Table

GNF-7

Cytoskeleton Compound Library

Anti-Alzheimer's Disease Compound Library

Anti-Blood Cancer Compound Library

Anti-Parkinson's Disease Compound Library

Neurodegenerative Disease-related Compound Library

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Publications Citing Use of MedChemExpress (MCE) GNF-7

Ver todos los productos específicos de isoformas Bcr-Abl

Actividad biológica

Chemical Information

Publications (2)

Solvente y solubilidad

Pureza y Documentación

Referencias

Help & FAQs

Complete Stock Solution Preparation Table

GNF-7 Related Classifications

HY-10943 Related Classifications