Cat. No.: HY-158062

LC-1-40

Name: LC-1-40
Brand: MedChemExpress
SKU: HY-158062
Price: 680.00 USD
Availability: InStock
Rating: 5 (1 reviews)

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Based on 1 Customer Validation

LC-1-40 is a selective NUDT1 PROTAC degrader with a DC₅₀ of 0.97 nM. LC-1-40 recruits NUDT1 to the CRBN E3 ubiquitin ligase complex, achieving degradation through a proteasome-dependent pathway. LC-1-40 leads to increased intratumoral nucleotide damage and cell Apoptosis. LC-1-40 can be used for research related to Mycn-amplified neuroblastoma.
(Pink: MTH1/NUDT1 ligand (HY-187054); Blue: Cereblon ligand (HY-W023573); Black: linker).

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

Purity : 99.65%
Formula: C₄₉H₄₈N₈O₆
Molecular Weight:844.96

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

LC-1-40 Chemical Structure

Size

Price

Stock

Quantity

Amount: USD 0.00

* Please select Quantity before adding items.

Top Publications Citing

Use of MCE Products

Fluorescent Dye

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

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

LC-1-40 is a selective NUDT1 PROTAC degrader with a DC₅₀ of 0.97 nM. LC-1-40 recruits NUDT1 to the CRBN E3 ubiquitin ligase complex, achieving degradation through a proteasome-dependent pathway. LC-1-40 leads to increased intratumoral nucleotide damage and cell Apoptosis. LC-1-40 can be used for research related to Mycn-amplified neuroblastoma^[1]. (Pink: MTH1/NUDT1 ligand (HY-187054); Blue: Cereblon ligand (HY-W023573); Black: linker).

IC₅₀ & Target

^[1]

Cereblon

All PROTACs Isoforms :

All DNA/RNA Synthesis Isoforms :

In Vitro

Anti-cancerOxidative StressOthers

Anti-cancer

LC-1-40 selectively kills tumor cells with high MYC/MYCN expression in a panel of tumor cell lines, without affecting cells with low MYC/MYCN expression^[1].

Oxidative Stress

LC-1-40 triggers MYCN-dependent synthetic lethality in SHEP MYCN-ER cells by inducing oxidative nucleotide accumulation and DNA damage, and this effect is irreversible under conditions of MYCN hyperactivation^[1].

Others

LC-1-40 (0.1-100 nM; 0.5-6 h) potently degrades NUDT1 in SHEP MYCN-ER cells, with a DC₅₀ of 0.97 nM and a D_max of 96% at 50 nM^[1].
LC-1-40 (50 nM; 6 h) degrades NUDT1 in SF188 cells via a CRBN- and proteasome-dependent PROTAC mechanism^[1].
LC-1-40 (100 nM; 6 h) selectively degrades NUDT1 in SF188 cells with minimal off-target effects on the global proteome^[1].
LC-1-40 (50 nM; 36 h) exerts cytotoxic activity in SHEP MYCN-ER cells that is strictly dependent on targeted degradation of NUDT1, as the degradation-resistant E77K mutant completely rescues cell death^[1].
LC-1-40 reduces NUDT1 protein levels in Kelly and SF188 cells but does not affect NUDT1 mRNA expression^[1].

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

Western Blot Analysis^[1]

Cell Line:

SF188 human glioblastoma cells
Concentration:

50 nM (LC-1-40); TH287/3-aminopiperidine-2,6-dione pretreatment (concentrations unspecified)
Incubation Time:

6 h (LC-1-40 incubation); 2 h (TH287/3-aminopiperidine-2,6-dione pretreatment)
Result:

Induced NUDT1 loss that was efficiently rescued by both TH287 and 3-aminopiperidine-2,6-dione.
Induced NUDT1 degradation that was rescued by MG132 (a 26S proteasome inhibitor).

Parmacokinetics

Species	Dose	Route	C_max	T_max	T_1/2	AUC_inf	F	CL	V_ss
Mice^[1]	5 mg/kg	i.v.	4373 ng/mL	0.08 h	6.34 h	32571 ng·h/mL	/	2.57 mL/min/kg	1.2 mL/kg
Mice^[1]	30 mg/kg	i.p.	3080 ng/mL	3.33 h	42.7 h	59799 ng·h/mL	32.7 %	/	/
Mice^[1]	30 mg/kg	p.o.	1923 ng/mL	3.33 h	7.13 h	25063 ng·h/mL	14.2 %	/	/

In Vivo

Anti-cancerApoptosis

Anti-cancer

LC-1-40 (30 mg/kg; i.p.; once daily), despite achieving NUDT1 depletion, does not significantly inhibit the growth of MYCN non-amplified donor-derived neuroblastoma xenografts^[1].

Anti-cancer

Apoptosis

LC-1-40 (30 mg/kg; i.p.; once daily) depletes intratumoral NUDT1 in mice and selectively inhibits the growth of MYCN-amplified neuroblastoma xenografts by inducing nucleotide damage and apoptosis^[1].

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

Animal Model:

NPG (female; 6-week-old; MYCN-amplified T409 primary neuroblastoma patient-derived xenograft)^[1]
Dosage:

30 mg/kg
Administration:

i.p.; daily
Result:

Caused remarkable intratumoral NUDT1 depletion within 1 h after a single i.p. dose.
Selectively impeded the growth of MYCN-amplified T409 tumors.
Led to increased intratumoral nucleotide damage and apoptosis, as quantified by 8-oxo-dG and cleaved-Caspase 3 staining.
Was well tolerated, with body weight sustained over the administration period.

Animal Model:

NPG (female; 6-week-old; MYCN-nonamplified T423 primary neuroblastoma patient-derived xenograft)^[1]
Dosage:

30 mg/kg
Administration:

i.p.; daily
Result:

Achieved similar NUDT1 depletion in MYCN-nonamplified T423 tumors.
Exhibited minimal effect on tumor growth.
Was well tolerated, with body weight sustained over the administration period.

Related Protocols :

Chemical Information

Appearance Solid
Molecular Weight 844.96
Formula C₄₉H₄₈N₈O₆
Color Light yellow to yellow
SMILES

O=C1CCC(C(N1)=O)N2C(C3=C(C2=O)C=C(C=C3)N4CCN(CC4)CC5CCN(CC5)C(C6=CC=C(C=C6)C7=CC=C8N=CC(C(NC9CC9)=O)=C(C8=C7)NC%10=CC=CC=C%10)=O)=O
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (118.35 mM; Need ultrasonic; 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

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.1835 mL

5.9174 mL

11.8349 mL

5 mM

0.2367 mL

1.1835 mL

2.3670 mL

10 mM

0.1183 mL

0.5917 mL

1.1835 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, 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.

Molarity Calculator

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

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 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 5 mg/mL (5.92 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 2

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

Solubility: ≥ 5 mg/mL (5.92 mM); Clear solution

This protocol yields a clear solution of ≥ 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 (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.

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

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (275 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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)

References

[1]. Ye M, et al. Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability. Nature communications. 2024 Mar 16;15(1):2377. [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, 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.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.1835 mL	5.9174 mL	11.8349 mL	29.5872 mL
	5 mM	0.2367 mL	1.1835 mL	2.3670 mL	5.9174 mL
	10 mM	0.1183 mL	0.5917 mL	1.1835 mL	2.9587 mL
	15 mM	0.0789 mL	0.3945 mL	0.7890 mL	1.9725 mL
	20 mM	0.0592 mL	0.2959 mL	0.5917 mL	1.4794 mL
	25 mM	0.0473 mL	0.2367 mL	0.4734 mL	1.1835 mL
	30 mM	0.0394 mL	0.1972 mL	0.3945 mL	0.9862 mL
	40 mM	0.0296 mL	0.1479 mL	0.2959 mL	0.7397 mL
	50 mM	0.0237 mL	0.1183 mL	0.2367 mL	0.5917 mL
	60 mM	0.0197 mL	0.0986 mL	0.1972 mL	0.4931 mL
	80 mM	0.0148 mL	0.0740 mL	0.1479 mL	0.3698 mL
	100 mM	0.0118 mL	0.0592 mL	0.1183 mL	0.2959 mL

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LC-1-40

All PROTACs Isoforms

All DNA/RNA Synthesis Isoforms