BLZ945
featured

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

MedKoo CAT#: 407110

CAS#: 953769-46-5 (free base)

Description: Sotuletinib, also known as BLZ945, is a potent and selective CSF-1R kinase inhibitor. BLZ945 showed effects of CSF1R inhibition on other tumor-infiltrating immune cells. BLZ945 attenuates the turnover rate of TAMs while increasing the number of CD8+ T cells that infiltrate cervical and breast carcinomas. BLZ945 decreases the growth of malignant cells in the mouse mammary tumor virus-driven polyomavirus middle T antigen (MMTV-PyMT) model of mammary carcinogenesis. BLZ945 prevents tumor progression in the keratin 14-expressing human papillomavirus type 16 (K14-HPV-16) transgenic model of cervical carcinogenesis.

Chemical Structure

img
BLZ945
CAS# 953769-46-5 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 407110
Name: BLZ945
CAS#: 953769-46-5 (free base)
Chemical Formula: C20H22N4O3S
Exact Mass: 398.14
Molecular Weight: 398.480
Elemental Analysis: C, 60.28; H, 5.57; N, 14.06; O, 12.04; S, 8.05

Price and Availability

Size Price Availability Quantity
25mg USD 90 Ready to ship
50mg USD 150 Ready to ship
100mg USD 250 Ready to ship
200mg USD 450 Ready to ship
500mg USD 950 Ready to ship
1g USD 1650 Ready to ship
2g USD 2950 Ready to ship
Bulk inquiry

Related CAS #: 2222138-40-9 (2HCl)   2222138-31-8 (HCl)   953769-46-5 (free base)    

Synonym: BLZ945; BLZ 945; BLZ-945.Sotuletinib;

IUPAC/Chemical Name: 4-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)oxy)-N-methylpicolinamide

InChi Key: ADZBMFGQQWPHMJ-RHSMWYFYSA-N

InChi Code: InChI=1S/C20H22N4O3S/c1-21-19(26)16-10-13(8-9-22-16)27-12-6-7-15-18(11-12)28-20(24-15)23-14-4-2-3-5-17(14)25/h6-11,14,17,25H,2-5H2,1H3,(H,21,26)(H,23,24)/t14-,17-/m1/s1

SMILES Code: O=C(NC)C1=NC=CC(OC2=CC3=C(N=C(N[C@@H]4CCCC[C@H]4O)S3)C=C2)=C1

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: BLZ945 is a CSF-1R (c-Fms) inhibitor with an IC50 of 1 nM.
In vitro activity: To uncover the essential factors contributing to the alterations in myelopoiesis, 28 soluble factors in tumor-conditioned media were ama;yzed and M-CSF was identified (Supplementary Fig. S3A and S3B) as the only factor that was absent in the culture medium but produced at high levels by all three tumor cell lines. Indeed, antagonizing CSF-1R during differentiation of CD34+ cells by a highly selective inhibitor (BLZ945) specifically limited the differentiation of macrophages and monocytes (Fig. 2D and Supplementary Fig. S3C) that had high expression of CSF-1R (Fig. 2E). However, it had no impact on DCs (Fig. 2D), because of their lower expression of CSF-1R (Supplementary Fig. S2E). Functionally, BLZ945 significantly recovered the potential of myeloid cells to stimulate T cells (Fig. 2F and 2G), with comparable effects on CD8+ and CD4+ subsets (Supplementary Fig. S3D and S3E). Notably, BLZ945 decreased monocytes and macrophages in cultures with only cytokines (Fig. 2D), but this did not lead to consistent changes of their T cell–activating capacities (Fig. 2F). Reference: Clin Cancer Res. 2016 Aug 1;22(15):3849-59. https://clincancerres.aacrjournals.org/content/22/15/3849.long
In vivo activity: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). While multiple effective immunomodulatory therapies for MS exist today, they lack the scope of promoting CNS repair, in particular remyelination. Microglia play a pivotal role in regulating myelination processes, and the colony-stimulating factor 1 (CSF-1) pathway is a key regulator for microglia differentiation and survival. Here, the effects of the CSF-1 receptor kinase inhibitor, BLZ945, on central myelination processes were investigated in the 5-week murine cuprizone model by non-invasive and longitudinal magnetic resonance imaging (MRI) and histology. Therapeutic 2-week BLZ945 treatment caused a brain region-specific enhancement of remyelination in the striatum/cortex, which was absent in the corpus callosum/external capsule. This beneficial effect correlated positively with microglia reduction, increased oligodendrocytes and astrogliosis. Reference: Acta Neuropathol Commun. 2018 Feb 15;6(1):9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815182/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 59.4 149.17
Ethanol 3.0 7.53
Water 1.0 2.51
DMF 25.0 62.74
DMF:PBS (pH 7.2) (1:8) 0.1 0.28

Preparing Stock Solutions

The following data is based on the product molecular weight 398.48 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. Mao Y, Eissler N, Blanc KL, Johnsen JI, Kogner P, Kiessling R. Targeting Suppressive Myeloid Cells Potentiates Checkpoint Inhibitors to Control Spontaneous Neuroblastoma. Clin Cancer Res. 2016 Aug 1;22(15):3849-59. doi: 10.1158/1078-0432.CCR-15-1912. Epub 2016 Mar 8. PMID: 26957560. 2. Beckmann N, Giorgetti E, Neuhaus A, Zurbruegg S, Accart N, Smith P, Perdoux J, Perrot L, Nash M, Desrayaud S, Wipfli P, Frieauff W, Shimshek DR. Brain region-specific enhancement of remyelination and prevention of demyelination by the CSF1R kinase inhibitor BLZ945. Acta Neuropathol Commun. 2018 Feb 15;6(1):9. doi: 10.1186/s40478-018-0510-8. PMID: 29448957; PMCID: PMC5815182.
In vitro protocol: 1. Mao Y, Eissler N, Blanc KL, Johnsen JI, Kogner P, Kiessling R. Targeting Suppressive Myeloid Cells Potentiates Checkpoint Inhibitors to Control Spontaneous Neuroblastoma. Clin Cancer Res. 2016 Aug 1;22(15):3849-59. doi: 10.1158/1078-0432.CCR-15-1912. Epub 2016 Mar 8. PMID: 26957560.
In vivo protocol: 1. Beckmann N, Giorgetti E, Neuhaus A, Zurbruegg S, Accart N, Smith P, Perdoux J, Perrot L, Nash M, Desrayaud S, Wipfli P, Frieauff W, Shimshek DR. Brain region-specific enhancement of remyelination and prevention of demyelination by the CSF1R kinase inhibitor BLZ945. Acta Neuropathol Commun. 2018 Feb 15;6(1):9. doi: 10.1186/s40478-018-0510-8. PMID: 29448957; PMCID: PMC5815182.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

: Zheng C, Zhong Q, Yi K, Kong H, Cao F, Zhuo C, Xu Y, Shi R, Ju E, Song W, Tao Y, Chen X, Li M. Anti-phagocytosis-blocking repolarization-resistant membrane- fusogenic liposome (ARMFUL) for adoptive cell immunotherapy. Sci Adv. 2023 Aug 9;9(32):eadh2413. doi: 10.1126/sciadv.adh2413. Epub 2023 Aug 9. PMID: 37556535; PMCID: PMC10411906.


2: Dye CN, Franceschelli D, Leuner B, Lenz KM. Microglia depletion facilitates the display of maternal behavior and alters activation of the maternal brain network in nulliparous female rats. Neuropsychopharmacology. 2023 Jun 17. doi: 10.1038/s41386-023-01624-1. Epub ahead of print. PMID: 37330580.


3: Huang Y, Yang C, Lv J, Zhang Y, Wang K, Ma L, Liu Z, Yu H, Li M, Tang Z. Formula optimization and in vivo study of poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4/BLZ945 nanoparticles for cancer therapy. Int J Pharm. 2023 Apr 5;636:122849. doi: 10.1016/j.ijpharm.2023.122849. Epub 2023 Mar 17. PMID: 36933582.


4: An X, Wang J, Tong L, Zhang X, Fu H, Zhang J, Xie H, Huang Y, Jia H. 18F-Labeled o‑aminopyridyl alkynyl radioligands targeting colony- stimulating factor 1 receptor for neuroinflammation imaging. Bioorg Med Chem. 2023 Apr 1;83:117233. doi: 10.1016/j.bmc.2023.117233. Epub 2023 Mar 8. PMID: 36933438.


5: Thongchot S, Duangkaew S, Yotchai W, Maungsomboon S, Phimolsarnti R, Asavamongkolkul A, Thuwajit P, Thuwajit C, Chandhanayingyong C. Novel CSF1R-positive tenosynovial giant cell tumor cell lines and their pexidartinib (PLX3397) and sotuletinib (BLZ945)-induced apoptosis. Hum Cell. 2023 Jan;36(1):456-467. doi: 10.1007/s13577-022-00823-0. Epub 2022 Dec 2. PMID: 36456782; PMCID: PMC9813176.


6: Kesarwani P, Kant S, Zhao Y, Miller CR, Chinnaiyan P. The Influence of the Ketogenic Diet on the Immune Tolerant Microenvironment in Glioblastoma. Cancers (Basel). 2022 Nov 11;14(22):5550. doi: 10.3390/cancers14225550. PMID: 36428642; PMCID: PMC9688691.


7: Pognan F, Buono C, Couttet P, Galarneau JR, Timsit Y, Wolf A. Liver enzyme delayed clearance in rat treated by CSF1 receptor specific antagonist Sotuletinib. Curr Res Toxicol. 2022 Oct 29;3:100091. doi: 10.1016/j.crtox.2022.100091. PMID: 36353522; PMCID: PMC9637862.


8: Chokr SM, Milinkeviciute G, Jimenez GA, Abubakr H, Cramer KS. Long-term microglia depletion impairs synapse elimination and auditory brainstem function. Sci Rep. 2022 Nov 2;12(1):18521. doi: 10.1038/s41598-022-23250-5. PMID: 36323869; PMCID: PMC9630367.


9: Xie X, Feng Y, Zhang H, Su Q, Song T, Yang G, Li N, Wei X, Li T, Qin X, Li S, Wu C, Zhang X, Wang G, Liu Y, Yang H. Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy. Bioact Mater. 2022 Mar 11;16:107-119. doi: 10.1016/j.bioactmat.2022.03.008. Erratum in: Bioact Mater. 2022 Sep 07;21:239-240. PMID: 35386322; PMCID: PMC8958467.


10: Hwang D, Seyedsadr MS, Ishikawa LLW, Boehm A, Sahin Z, Casella G, Jang S, Gonzalez MV, Garifallou JP, Hakonarson H, Zhang W, Xiao D, Rostami A, Zhang GX, Ciric B. CSF-1 maintains pathogenic but not homeostatic myeloid cells in the central nervous system during autoimmune neuroinflammation. Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2111804119. doi: 10.1073/pnas.2111804119. Epub 2022 Mar 30. PMID: 35353625; PMCID: PMC9168454.


11: Kosti CN, Vaitsi PC, Pappas AG, Iliopoulou MP, Psarra KK, Magkouta SF, Kalomenidis IT. CSF1/CSF1R signaling mediates malignant pleural effusion formation. JCI Insight. 2022 Mar 22;7(6):e155300. doi: 10.1172/jci.insight.155300. PMID: 35315360; PMCID: PMC8986064.


12: Klemm F, Möckl A, Salamero-Boix A, Alekseeva T, Schäffer A, Schulz M, Niesel K, Maas RR, Groth M, Elie BT, Bowman RL, Hegi ME, Daniel RT, Zeiner PS, Zinke J, Harter PN, Plate KH, Joyce JA, Sevenich L. Compensatory CSF2-driven macrophage activation promotes adaptive resistance to CSF1R inhibition in breast-to-brain metastasis. Nat Cancer. 2021 Oct;2(10):1086-1101. doi: 10.1038/s43018-021-00254-0. Epub 2021 Oct 18. PMID: 35121879.


13: Borse V, Kaur T, Hinton A, Ohlemiller K, Warchol ME. Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea. Front Cell Dev Biol. 2021 Dec 9;9:777836. doi: 10.3389/fcell.2021.777836. PMID: 34957108; PMCID: PMC8696258.


14: Wies Mancini VSB, Di Pietro AA, de Olmos S, Silva Pinto P, Vence M, Marder M, Igaz LM, Marcora MS, Pasquini JM, Correale JD, Pasquini LA. Colony- stimulating factor-1 receptor inhibition attenuates microgliosis and myelin loss but exacerbates neurodegeneration in the chronic cuprizone model. J Neurochem. 2022 Mar;160(6):643-661. doi: 10.1111/jnc.15566. Epub 2022 Jan 9. PMID: 34935149.


15: Sun X, Zhang J, Zhao X, Yang C, Shi M, Zhang B, Hu H, Qiao M, Chen D, Zhao X. Binary regulation of the tumor microenvironment by a pH-responsive reversible shielding nanoplatform for improved tumor chemo-immunotherapy. Acta Biomater. 2022 Jan 15;138:505-517. doi: 10.1016/j.actbio.2021.11.017. Epub 2021 Nov 16. PMID: 34798317.


16: Pfirschke C, Zilionis R, Engblom C, Messemaker M, Zou AE, Rickelt S, Gort- Freitas NA, Lin Y, Bill R, Siwicki M, Gungabeesoon J, Sprachman MM, Marquard AN, Rodell CB, Cuccarese MF, Quintana J, Ahmed MS, Kohler RH, Savova V, Weissleder R, Klein AM, Pittet MJ. Macrophage-Targeted Therapy Unlocks Antitumoral Cross- talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells. Cancer Immunol Res. 2022 Jan;10(1):40-55. doi: 10.1158/2326-6066.CIR-21-0326. Epub 2021 Dec 1. PMID: 34795032; PMCID: PMC10132467.


17: van der Wildt B, Miao Z, Reyes ST, Park JH, Klockow JL, Zhao N, Romero A, Guo SG, Shen B, Windhorst AD, Chin FT. BLZ945 derivatives for PET imaging of colony stimulating factor-1 receptors in the brain. Nucl Med Biol. 2021 Sep- Oct;100-101:44-51. doi: 10.1016/j.nucmedbio.2021.06.005. Epub 2021 Jun 23. PMID: 34174546.


18: Fang Y, He Y, Wu C, Zhang M, Gu Z, Zhang J, Liu E, Xu Q, Asrorov AM, Huang Y. Magnetism-mediated targeting hyperthermia-immunotherapy in "cold" tumor with CSF1R inhibitor. Theranostics. 2021 May 3;11(14):6860-6872. doi: 10.7150/thno.57511. PMID: 34093858; PMCID: PMC8171105.


19: Magkouta SF, Vaitsi PC, Pappas AG, Iliopoulou M, Kosti CN, Psarra K, Kalomenidis IT. CSF1/CSF1R Axis Blockade Limits Mesothelioma and Enhances Efficiency of Anti-PDL1 Immunotherapy. Cancers (Basel). 2021 May 22;13(11):2546. doi: 10.3390/cancers13112546. PMID: 34067348; PMCID: PMC8196870.


20: Liaw K, Reddy R, Sharma A, Li J, Chang M, Sharma R, Salazar S, Kannan S, Kannan RM. Targeted systemic dendrimer delivery of CSF-1R inhibitor to tumor- associated macrophages improves outcomes in orthotopic glioblastoma. Bioeng Transl Med. 2020 Dec 11;6(2):e10205. doi: 10.1002/btm2.10205. PMID: 34027092; PMCID: PMC8126814.

Almahariq MF, Quinn TJ, Kesarwani P, Kant S, Miller CR, Chinnaiyan P. Inhibition of Colony-Stimulating Factor-1 Receptor Enhances the Efficacy of Radiotherapy and Reduces Immune Suppression in Glioblastoma. In Vivo. 2021 Jan-Feb;35(1):119-129. doi: 10.21873/invivo.12239. PMID: 33402457; PMCID: PMC7880776.