PROTAC KRAS G12D degrader 1

Name: PROTAC KRAS G12D degrader 1
Brand: MedChemExpress
SKU: HY-161176
Rating: 4.5 (0 reviews)

Cat. No.: HY-161176 Purity: 98.32%: Data Sheet
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PROTAC KRAS G12D degrader 1 is a selective PROTAC KRAS^G12D degrader. PROTAC KRAS G12D degrader 1 inhibits proliferation of KRAS^G12D-mutant cells and suppresses ERK phosphorylation. PROTAC KRAS G12D degrader 1 inhibits tumor growth in mice bearing AsPC-1 xenografts. PROTAC KRAS G12D degrader 1 can be used for the study of KRAS^G12D-driven cancers.(Pink: KRAS ligand (HY-175892), Blue: VHL Ligand (HY-112078), Black: Linker, E3 ligase ligand-linker conjugate (HY-175893)).
(Pink: KRas G12D Target protein ligand; Blue: VHL ligand (HY-112078); Black: linker).

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

PROTAC KRAS G12D degrader 1 Chemical Structure

CAS No. : 3033583-54-6

Size	Stock	Quantity
1 mg	In-stock	Estimated Time of Arrival: December 31
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
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•Related Screening Libraries:

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von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

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View All Isoforms

K-Ras H-Ras N-Ras Ras

View All ERK Isoform Specific Products:

View All Isoforms

ERK ERK1 ERK2 ERK5 ERK8

Biological Activity
Purity & Documentation
References
Customer Review

Description

PROTAC KRAS G12D degrader 1 is a selective PROTAC KRAS^G12D degrader. PROTAC KRAS G12D degrader 1 inhibits proliferation of KRAS^G12D-mutant cells and suppresses ERK phosphorylation. PROTAC KRAS G12D degrader 1 inhibits tumor growth in mice bearing AsPC-1 xenografts. PROTAC KRAS G12D degrader 1 can be used for the study of KRAS^G12D-driven cancers.(Pink: KRAS ligand (HY-175892), Blue: VHL Ligand (HY-112078), Black: Linker, E3 ligase ligand-linker conjugate (HY-175893))^[1]. (Pink: KRas G12D Target protein ligand; Blue: VHL ligand (HY-112078); Black: linker).

IC₅₀ & Target^[1]

VHL

KRas G12D

Cellular Effect

Cell Line	Type	Value	Description	References
AGS	IC₅₀	31.36 nM Compound: 8o	Antiproliferative activity against human AGS cells harboring KRAS G12D mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay Antiproliferative activity against human AGS cells harboring KRAS G12D mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay	[PMID: 38197882]
ASPC1	IC₅₀	231.2 nM Compound: 8o	Antiproliferative activity against human ASPC1 cells assessed as inhibition of cell viability incubated for 6 hrs followed by compound washout measured after 114 hrs by Cell Titer Glo assay Antiproliferative activity against human ASPC1 cells assessed as inhibition of cell viability incubated for 6 hrs followed by compound washout measured after 114 hrs by Cell Titer Glo assay	[PMID: 38197882]
ASPC1	IC₅₀	59.97 nM Compound: 8o	Antiproliferative activity against human ASPC1 cells harboring KRAS G12D mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay Antiproliferative activity against human ASPC1 cells harboring KRAS G12D mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay	[PMID: 38197882]
ASPC1	IC₅₀	61.14 nM Compound: 8o	Antiproliferative activity against human ASPC1 cells assessed as inhibition of cell viability incubated for 120 hrs of continuous treatment by Cell Titer Glo assay Antiproliferative activity against human ASPC1 cells assessed as inhibition of cell viability incubated for 120 hrs of continuous treatment by Cell Titer Glo assay	[PMID: 38197882]
HPAF-II	IC₅₀	45.22 nM Compound: 8o	Antiproliferative activity against human HPAF-II cells harboring KRAS G12D mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay Antiproliferative activity against human HPAF-II cells harboring KRAS G12D mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay	[PMID: 38197882]
NCI-H1975	IC₅₀	> 10000 nM Compound: 8o	Antiproliferative activity against human NCI-H1975 cells harboring wild-type KRAS assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay Antiproliferative activity against human NCI-H1975 cells harboring wild-type KRAS assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay	[PMID: 38197882]
NCI-H358	IC₅₀	> 9000 nM Compound: 8o	Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay	[PMID: 38197882]
SNU1	IC₅₀	43.51 nM Compound: 8o	Antiproliferative activity against human SNU1 cells harboring KRAS G12D mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay Antiproliferative activity against human SNU1 cells harboring KRAS G12D mutant assessed as inhibition of cell viability incubated for 5 days by Cell Titer Glo assay	[PMID: 38197882]

In Vitro

PROTAC KRAS G12D degrader 1 (Compound 8o) (24 h) dose-dependently degrades KRAS^G12D in SNU-1, HPAF-II, AGS, and PANC 04.03 cells (heterozygous KRAS^G12D) with DC₅₀ values of 19.77 nM, 52.96 nM, 7.49 nM, and 87.8 nM, respectively^[1].
PROTAC KRAS G12D degrader 1 (1 μM, 1-24 h) significantly decreases KRAS^G12D protein level in AsPC-1 cells^[1].
PROTAC KRAS G12D degrader 15 days) inhibits the proliferation of KRAS^G12D mutant cells including AsPC-1, SNU-1, HPAF-II, AGS, and PANC 04.03 with IC₅₀ values of 59.97 nM, 43.51 nM, 31.36 nM, 51.53 nM, and >10000 nM, respectively^[1].
PROTAC KRAS G12D degrader 1 (1 μM, 6 h) leads to sustained KRAS^G12D degradation and pERK inhibition in AsPC-1 cells^[1].

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

In Vivo

PROTAC KRAS G12D degrader 1 (Compound 8o) (50 mg/kg, s.c., once daily or every three days, 22 days) inhibits tumor growth in BALB/c nude mice bearing AsPC-1 xenografts^[1].

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

Animal Model:	AsPC-1 cells (5 × 10⁶ in 100 µL) were subcutaneously implanted into the flanks of 8-9-week-old BALB/c nude mice^[1]
Dosage:	50 mg/kg
Administration:	s.c., once daily or every three days, 22 days
Result:	Achieved tumor growth inhibition. Reduced KRAS^G12D protein level and the phosphorylation level of ERK in AsPC-1 xenograft tumor tissues. Downregulated the mRNA level of DUSP4. Showed no significant changes in body weight.

Molecular Weight

1103.33

Formula

C₅₉H₇₂F₂N₁₀O₇S

CAS No.

3033583-54-6

Appearance

Solid

Color

Off-white to light yellow

SMILES

FC1=C(CC)C2=C(C3=NC=C4C(N=C(OC[C@@H]5CCCN5CCCCOCC(N[C@@H](C(C)(C)C)C(N6[C@H](C(N[C@@H](C)C7=CC=C(C8=C(C)N=CS8)C=C7)=O)C[C@@H](O)C6)=O)=O)N=C4N9C[C@H]%10N[C@H](CC%10)C9)=C3F)C=C(O)C=C2C=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

In Vitro:

DMSO : 10 mg/mL (9.06 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)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	0.9063 mL	4.5317 mL	9.0635 mL
5 mM	0.1813 mL	0.9063 mL	1.8127 mL
10 mM	---	---	---

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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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In Vivo Dissolution Calculator

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Purity & Documentation

Purity: 98.32%

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Data Sheet (272 KB) SDS (251 KB)

COA (247 KB) HNMR (335 KB) RP-HPLC (169 KB) LCMS (234 KB)

Handling Instructions (2659 KB)

References

[1]. Zhou C, et al. Design, Synthesis, and Biological Evaluation of Potent and Selective PROTAC Degraders of Oncogenic KRASG12D. J Med Chem. 2024 Jan 10. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	0.9063 mL	4.5317 mL	9.0635 mL	22.6587 mL
DMSO	5 mM	0.1813 mL	0.9063 mL	1.8127 mL	4.5317 mL