ML414 | CAS#790702-57-7 | OST inhibitor

MedKoo Cat#: 561059 | Name: ML414

Description:

WARNING: This product is for research use only, not for human or veterinary use.

NGI-1, also known s ML414, is a cell-permeable inhibitor of oligosaccharyltransferase (OST). In non-small-cell lung cancer cell lines that are dependent on EGFR, OST inhibition causes cell-cycle arrest accompanied by induction of p21, autofluorescence, and cell morphology changes.

Chemical Structure

ML414

CAS#790702-57-7

Theoretical Analysis

MedKoo Cat#: 561059

Name: ML414

CAS#: 790702-57-7

Chemical Formula: C17H22N4O3S2

Exact Mass: 394.1133

Molecular Weight: 394.51

Elemental Analysis: C, 51.76; H, 5.62; N, 14.20; O, 12.17; S, 16.25

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to Ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,850.00	Ready to ship
1g	USD 4,250.00	Ready to ship

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Related CAS #

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Synonym

NGI-1; NGI1; NGI 1; ML414; ML 414; ML-414;

IUPAC/Chemical Name

5-(dimethylsulfamoyl)-N-(5-methyl-1,3-thiazol-2-yl)-2-(pyrrolidin-1-yl)benzamide

InChi Key

QPKGRLIYJGBKJL-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H22N4O3S2/c1-12-11-18-17(25-12)19-16(22)14-10-13(26(23,24)20(2)3)6-7-15(14)21-8-4-5-9-21/h6-7,10-11H,4-5,8-9H2,1-3H3,(H,18,19,22)

SMILES Code

O=C(NC1=NC=C(C)S1)C2=CC(S(=O)(N(C)C)=O)=CC=C2N3CCCC3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C21R02B10

QC Data

View QC data: current batch, Lot#C21R02B10

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

NGI-1 (ML414) is a potent oligosaccharyltransferase (OST) inhibitor, directly targeting and blocking the function of the OST catalytic subunits STT3A and STT3B

In vitro activity:

WT HEK, STT3A-KO, and STT3B-KO cells were infected with HSV-1 in the absence or presence of NGI-1 or C19, for pfu assays on Vero cell monolayers. over the general range (1–5 μM) that suppressed N-glycosylation, NGI-1 inhibited HSV-1 function in all 3 lines. Interestingly, NGI-1 suppressed infectivity most potently when STT3B-OST was ablated. Sensitivity of infectivity to NGI-1 did not have an obvious correlation with effects of NGI-1 on envelope protein glycosylation. Glycoform quantitation (glycosylation indices) in both Fig. 2C (MOI = 1–2) and Fig. 4 (MOI = 0.1) showed that 2 μM NGI-1 treatment of STT3A-KO cells resulted in more total loss of gC and gD N-glycosylation than with similarly treated STT3B-KO cells. However, the net suppression of gC and gD Nglycosylation by 2 μM NGI-1 treatment compared to DMSO controls was at least as strong for STT3A-KO cells as for STT3B-KO cells. These results reaffirmed that NGI-1 can inhibit both STT3A-OST and STT3B-OST in HSV-1–infected HEK293 cells and that STT3A-OST is of primary importance for gC and gD N-glycosylation. Reference: FASEB J. 2019 Jun; 33(6): 6801–6812. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529348/

In vivo activity:

To assess the effect of NGI-1 on xenograft tumor growth, an NGI-1 nanoparticle formulation that overcomes the low solubility of this compound was used. First the effect of NGI-NPs were tested using D54-ERLucT xenografts, which increase biolouminescence after inhibition of glycoyslation (17). A significant induction of bioluminescence was found in mice that received NGI-1 at both 24 (1.7 fold, p =.03; Fig. 5A) and 48 hour (1.7 fold, p =.03; Fig. 5A) time points. Tunicmaycin, another inhibidor of N-linked glycosylation was used as a positive control and induced bioluminescence (4.2 fold at 24 hours (p =.007)). These results confirmed the ability of NGI-1 NPs to inhibit glycosylation in D54 tumors in vivo. Reference: Clin Cancer Res. 2019 Jan 15; 25(2): 784–795. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314911/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	57.0	144.63

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 394.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Lu H, Cherepanova NA, Gilmore R, Contessa JN, Lehrman MA. Targeting STT3A-oligosaccharyltransferase with NGI-1 causes herpes simplex virus 1 dysfunction. FASEB J. 2019 Jun;33(6):6801-6812. doi: 10.1096/fj.201802044RR. Epub 2019 Feb 27. PMID: 30811219; PMCID: PMC6529348. 2. Lopez-Sambrooks C, Shrimal S, Khodier C, Flaherty DP, Rinis N, Charest JC, Gao N, Zhao P, Wells L, Lewis TA, Lehrman MA, Gilmore R, Golden JE, Contessa JN. Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells. Nat Chem Biol. 2016 Dec;12(12):1023-1030. doi: 10.1038/nchembio.2194. Epub 2016 Oct 3. PMID: 27694802; PMCID: PMC5393272. 3. Baro M, Lopez Sambrooks C, Quijano A, Saltzman WM, Contessa J. Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity. Clin Cancer Res. 2019 Jan 15;25(2):784-795. doi: 10.1158/10780432.CCR-18-0792. Epub 2018 Jul 2. PMID: 29967251; PMCID: PMC6314911. 4. Wahl DR, Lawrence TS. No Sugar Added: A New Strategy to Inhibit Glioblastoma Receptor Tyrosine Kinases. Clin Cancer Res. 2019 Jan 15;25(2):455-456. doi: 10.1158/1078-0432.CCR-18-2113. Epub 2018 Sep 4. PMID: 30181388.

In vitro protocol:

In vivo protocol:

1. Baro M, Lopez Sambrooks C, Quijano A, Saltzman WM, Contessa J. Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity. Clin Cancer Res. 2019 Jan 15;25(2):784-795. doi: 10.1158/10780432.CCR-18-0792. Epub 2018 Jul 2. PMID: 29967251; PMCID: PMC6314911. 2. Wahl DR, Lawrence TS. No Sugar Added: A New Strategy to Inhibit Glioblastoma Receptor Tyrosine Kinases. Clin Cancer Res. 2019 Jan 15;25(2):455-456. doi: 10.1158/1078-0432.CCR-18-2113. Epub 2018 Sep 4. PMID: 30181388.

1: Lopez-Sambrooks C, Shrimal S, Khodier C, Flaherty DP, Rinis N, Charest JC, Gao N, Zhao P, Wells L, Lewis TA, Lehrman MA, Gilmore R, Golden JE, Contessa JN. Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells. Nat Chem Biol. 2016 Dec;12(12):1023-1030. doi: 10.1038/nchembio.2194. Epub 2016 Oct 3. PubMed PMID: 27694802; PubMed Central PMCID: PMC5393272.