LDC1267
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MedKoo CAT#: 407188

CAS#: 1361030-48-9

Description: LDC1267 is a potent and selective TAM kinase inhibitor. LDC1267 displays lower activity against Met, Aurora B, Lck, Src, and CDK8. LDC1267 markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo.


Chemical Structure

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LDC1267
CAS# 1361030-48-9

Theoretical Analysis

MedKoo Cat#: 407188
Name: LDC1267
CAS#: 1361030-48-9
Chemical Formula: C30H26F2N4O5
Exact Mass: 560.19
Molecular Weight: 560.560
Elemental Analysis: C, 64.28; H, 4.68; F, 6.78; N, 10.00; O, 14.27

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 400 Ready to ship
100mg USD 700 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2550 Ready to ship
1g USD 3850 Ready to ship
2g USD 6250 Ready to ship
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Synonym: LDC1267; LDC-1267; LDC 1267.

IUPAC/Chemical Name: N-[4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluoro-phenyl]-4-ethoxy-1-(4-fluoro-2-methyl-phenyl)pyrazole-3-carboxamide

InChi Key: ISPBCAXOSOLFME-UHFFFAOYSA-N

InChi Code: InChI=1S/C30H26F2N4O5/c1-5-40-28-16-36(23-8-6-18(31)12-17(23)2)35-29(28)30(37)34-19-7-9-25(21(32)13-19)41-24-10-11-33-22-15-27(39-4)26(38-3)14-20(22)24/h6-16H,5H2,1-4H3,(H,34,37)

SMILES Code: O=C(C1=NN(C2=CC=C(F)C=C2C)C=C1OCC)NC3=CC=C(OC4=CC=NC5=CC(OC)=C(OC)C=C45)C(F)=C3

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, not in water

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:

Biological target: LDC1267 is a highly selective TAM (Tyro3, Axl and Mer) kinase inhibitor with IC50s of <5 nM/8 nM/29 nM for Tyro3,Axl and Mer respectively.
In vitro activity: To assess whether modulation of the TAM/Cbl-b inhibitory pathway could be used for anti-tumor immunotherapy, a highly selective TAM kinase inhibitor, termed LDC1267. LDC1267 was developed and preferentially inhibits Tyro3, Axl, and Mer at low nanomolarity, as determined by tracer-based binding assays (Fig. 3d,e). Selectivity of LDC1267 was further assessed using a cell-free KINOMEscan assay covering 456 kinases (Fig. 3f, Supplementary Table 1). Cellular selectivity was confirmed employing a quantitative chemical proteomics approach, cell-based phosphorylation, and proliferation assays (Extended Data Fig. 9a-d). Treatment of NKG2D-activated NK cells with LDC1267 indeed abolished the inhibitory effects of Gas6 stimulation; LDC1267 had no apparent additional effect in Cbl-b deficient NK cells (Fig. 3g). Reference: Nature. 2014 Mar 27; 507(7493): 508–512. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258903/
In vivo activity: In vivo, wild-type mice treated with LDC1267 showed enhanced cytotoxicity towards RMA cells overexpressing the NKGD2 ligand Rae-1 (RMA-Rae1) to the same extent as C373AKI/KI mice, but had no effect on the already enhanced NK cytotoxicity in Cbl-bdeficient mice (Fig. 3h; Extended Data 9e). To provide definitive proof that LDC1267 treatment can license NK cells to kill, B16F10 melanoma-bearing mice were treated with NK cells that were either untreated or treated ex vivo with our TAM inhibitor (Extended Data Fig. 9f). Adoptive transfer of LDC1267-treated wild-type NK cells significantly increased the anti-tumor response to levels observed in mice transplanted with Cbl-b-/- NK cells, but did not increase the anti-metastatic efficacy of Cbl-b knock-out NK cells (Fig. 3i), reinforcing the notion that Cbl-b acts downstream of TAM receptors for NK cell inhibition. These results indicate that TAM receptor inhibition using LDC1267 unleashes NK cells to kill tumors cells in vivo. Reference: Nature. 2014 Mar 27; 507(7493): 508–512. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258903/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 89.20

Preparing Stock Solutions

The following data is based on the product molecular weight 560.56 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.

Recalculate based on batch purity %
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. Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I, Loeser S, Jamieson AM, Langdon WY, Ikeda F, Fededa JP, Cronin SJ, Nitsch R, Schultz-Fademrecht C, Eickhoff J, Menninger S, Unger A, Torka R, Gruber T, Hinterleitner R, Baier G, Wolf D, Ullrich A, Klebl BM, Penninger JM. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12. doi: 10.1038/nature12998. Epub 2014 Feb 19. PMID: 24553136; PMCID: PMC6258903. 2. Zou Z, Sun J, Kang Z, Wang Y, Zhao H, Zhu K, Wang J. Tyrosine Kinase Receptors Axl and MerTK Mediate the Beneficial Effect of Electroacupuncture in a Cuprizone-Induced Demyelinating Model. Evid Based Complement Alternat Med. 2020 Jul 4;2020:3205176. doi: 10.1155/2020/3205176. PMID: 32714402; PMCID: PMC7355344. 2
In vitro protocol: 1. Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I, Loeser S, Jamieson AM, Langdon WY, Ikeda F, Fededa JP, Cronin SJ, Nitsch R, Schultz-Fademrecht C, Eickhoff J, Menninger S, Unger A, Torka R, Gruber T, Hinterleitner R, Baier G, Wolf D, Ullrich A, Klebl BM, Penninger JM. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12. doi: 10.1038/nature12998. Epub 2014 Feb 19. PMID: 24553136; PMCID: PMC6258903.
In vivo protocol: 1. Zou Z, Sun J, Kang Z, Wang Y, Zhao H, Zhu K, Wang J. Tyrosine Kinase Receptors Axl and MerTK Mediate the Beneficial Effect of Electroacupuncture in a Cuprizone-Induced Demyelinating Model. Evid Based Complement Alternat Med. 2020 Jul 4;2020:3205176. doi: 10.1155/2020/3205176. PMID: 32714402; PMCID: PMC7355344. 2. Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I, Loeser S, Jamieson AM, Langdon WY, Ikeda F, Fededa JP, Cronin SJ, Nitsch R, Schultz-Fademrecht C, Eickhoff J, Menninger S, Unger A, Torka R, Gruber T, Hinterleitner R, Baier G, Wolf D, Ullrich A, Klebl BM, Penninger JM. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12. doi: 10.1038/nature12998. Epub 2014 Feb 19. PMID: 24553136; PMCID: PMC6258903.

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1: Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I, Loeser S, Jamieson
AM, Langdon WY, Ikeda F, Fededa JP, Cronin SJ, Nitsch R, Schultz-Fademrecht C,
Eickhoff J, Menninger S, Unger A, Torka R, Gruber T, Hinterleitner R, Baier G,
Wolf D, Ullrich A, Klebl BM, Penninger JM. The E3 ligase Cbl-b and TAM receptors
regulate cancer metastasis via natural killer cells. Nature. 2014 Mar
27;507(7493):508-12. doi: 10.1038/nature12998. Epub 2014 Feb 19. PubMed PMID:
24553136.