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Art. -Nr.: HY-173250

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YN14-H

YN14-H is a potent mutant KRAS^G12C PROTAC degrader. The DC₅₀ values of YN14-H in NCI-H358 and MIA PaCa-2 cells are 28.9 nM and 18.1 nM, respectively, with corresponding IC₅₀ values of 42 nM and 21 nM. YN14-H degrades KRAS^G12C in a ubiquitin-proteasome system-dependent manner, thereby significantly inducing apoptosis and inhibiting cell migration. YN14-H can be used for targeting tumors with KRAS^G12C mutations (such as non-small cell lung cancer, pancreatic cancer, etc.).
(Pink: KRas G12C ligand (HY-173252); Blue: VHL ligand (HY-125905); Black: linker).

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Formel: C₆₅H₇₈F₃N₁₁O₈S
Molecular Weight:1230.44

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (285 KB)

YN14-H Chemical Structure

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Use of MCE Products

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

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

YN14-H is a potent mutant KRAS^G12C PROTAC degrader. The DC₅₀ values of YN14-H in NCI-H358 and MIA PaCa-2 cells are 28.9 nM and 18.1 nM, respectively, with corresponding IC₅₀ values of 42 nM and 21 nM. YN14-H degrades KRAS^G12C in a ubiquitin-proteasome system-dependent manner, thereby significantly inducing apoptosis and inhibiting cell migration. YN14-H can be used for targeting tumors with KRAS^G12C mutations (such as non-small cell lung cancer, pancreatic cancer, etc.)^[1]. (Pink: KRas G12C ligand (HY-173252); Blue: VHL ligand (HY-125905); Black: linker).

IC₅₀ & Target^[1]

KRAS(G12C)

28.9 nM (DC₅₀, NCI-H358)

KRAS(G12C)

18.1 nM (DC₅₀, MIA PaCa-2)

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In Vitro

YN14-H (500 ns) promotes the formation of more stable interactions in the KRAS^G12C-VHL ternary complex, which is evidenced by a binding free energy of -158.12 kJ/mol and the presence of 10 stable hydrogen-bond interactions between the two proteins^[1].
YN14-H (0.01 nM-1 μM) induces the formation of the KRAS^G12C-VHL ternary complex with high affinity, with a dissociation constant K_d of 18.8 nM^[1].
YN14-H (0-5 μM) potently induces the KRAS^G12C-VHL protein-protein interaction, which is validated by a strong relative AlphaScreen luminescent signal^[1].
YN14-H (1 μM; 8 h) most effectively promotes the interaction between endogenous KRAS^G12C and VHL in NCI-H358 cells^[1].
YN14-H (1 nM-10 μM; 72 h) potently degrades KRAS^G12C protein in NCI-H358 and MIA PaCa-2 cells, with a DC₅₀ of 28.9 nmol/L in the former and 18.1 nmol/L in the latter, and achieves a maximal degradation rate of over 95% in both cell types^[1].
YN14-H (0-10 μM; 72 h) potently inhibits the proliferation of NCI-H358 (IC₅₀ = 0.042 μmol/L) and MIA PaCa-2 (IC₅₀ = 0.021 μmol/L) cells, whereas it exhibits no cytotoxicity in non-KRAS^G12C cells even at concentrations up to 10 μmol/L^[1].
YN14-H (0.01-1 μM; 48 h) potently inhibits the levels of phosphorylated AKT and ERK in a concentration-dependent manner in NCI-H358 and MIA PaCa-2 cells^[1].
YN14-H (100 nM; 12 h) potently inhibits the migratory capacity of NCI-H358 and MIA PaCa-2 cells^[1].
YN14-H (100 nM; 48 h) induces apoptosis in 35.19% of NCI-H358 cells and 55.19% of MIA PaCa-2 cells, and its efficacy is superior to that of other tested degraders^[1].

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

Western Blot Analysis^[1]

Cell Line:

NCI-H358 and MIA PaCa-2
Concentration:

1 nM, 3.3 nM, 10 nM, 33 nM, 100 nM, 330 nM, 1 μM, 3.3 μM, 10 μM
Incubation Time:

72 h
Result:

Significantly degraded the KRAS^G12C protein in a concentration-dependent manner, with a maximum degradation rate exceeding 98%.

Western Blot Analysis^[1]

Cell Line:

NCI-H358 and MIA PaCa-2
Concentration:

0.01, 0.1, 1 μM
Incubation Time:

48 h
Result:

Significantly inhibited the phosphorylation of downstream signaling molecules AKT and ERK in a concentration-dependent manner.

Apoptosis Analysis^[1]

Cell Line:

NCI-H358 and MIA PaCa-2
Concentration:

100 nM
Incubation Time:

48 h
Result:

Significantly induced apoptosis in both tumor cell lines, demonstrating superior pro-apoptotic ability compared to other tested compounds.

Cell Migration Assay ^[1]

Cell Line:

NCI-H358 and MIA PaCa-2
Concentration:

100 nM
Incubation Time:

12 h
Result:

Significantly inhibited the migration and wound closure of tumor cells.

Parmacokinetics

Species	Dose	Route	T_1/2	T_max	C_max	AUC_0-t	AUC_0-∞	MRT_0-∞
Mice^[1]	10 mg/kg	i.p.	8.81 h	1.0 h	934.01 ng/mL	3588.29 ng·h/mL	3615.73 ng·h/mL	5.92 h
Mice^[1]	30 mg/kg	i.p.	11.03 h	0.80 h	1090.66 ng/mL	9156.32 ng·h/mL	9682.21 ng·h/mL	14.20 h

In Vivo

YN14-H (10-30 mg/kg; i.p.; daily; 20 days) exhibits potent in vivo antitumor activity in KRAS^G12C-mutant NCI-H358 xenografts, achieving 88.68% TGI at 10 mg/kg and complete tumor regression at 30 mg/kg with no observed toxicity^[1].

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

Animal Model:

BALB/c nude (male, xenograft model with 5 x 10⁶ NCI-H358 cells)^[1]
Dosage:

10 mg/kg; 30 mg/kg
Administration:

i.p.; once daily; 20 days
Result:

Achieved a tumor growth inhibition (TGI) rate of 88.68% at 10 mg/kg at 14 days post-treatment.
Induced marked tumor regression with a TGI of 95.4% at 30 mg/kg at 14 days post-treatment.
Reduced tumor volume to approximately 500 mm³ in the 10 mg/kg group by day 20.
Caused complete tumor regression in the 30 mg/kg group by day 20.
Reduced KRASG12C protein levels in tumor tissue to a greater extent than YN14 at matching doses.
Reduced the percentage of Ki67-positive and CD31-positive tumor cells with greater potency than YN14 at matching doses.
Increased the percentage of cleaved caspase 3-positive tumor cells with greater potency than YN14 at matching doses.
Showed no obvious body weight loss or toxic signs during treatment.

Chemical Information

Molecular Weight 1230.44
Formel C₆₅H₇₈F₃N₁₁O₈S
SMILES

O=C([C@H]1N(C([C@@H](NC(C2(F)CC2)=O)C(C)(C)C)=O)C[C@H](O)C1)NCC3=CC=C(C4=C(C)N=CS4)C=C3OCCCN5CCC(COC6=CC=CC(F)=C6C7=C(F)C=C(C(N8[C@@H](C)CN(C(C=C)=O)CC8)=N9)C(N(C%10=C(C)C=CN=C%10C(C)C)C9=O)=N7)CC5
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (285 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Sun, et al. "Rational design of VHL-recruiting KRASG12C proteolysis-targeting chimeras based on molecular dynamics simulation." Chinese Chemical Letters (2025): 110992.

Calculators

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

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.

Bioz

Keywords

MOQ

Minimum order quantity

100 mg

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise

Produktname:
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YN14-H

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle Ras Isoform-spezifische Produkte anzeigen