LDN-193189 HCl | CAS#1435934-00-1 | BMP inhibitor

MedKoo Cat#: 598524 | Name: LDN-193189 HCl

Description:

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

LDN-193189 is a highly potent small molecule BMP inhibitor with IC50 of 5 and 30 nM for ALK2 and ALK3, respectively. LDN193189 also inhibits BMP type I receptors ALK6 (TGFβ1/BMP signaling) and subsequent SMAD phosphorylation.

Chemical Structure

LDN-193189 HCl

CAS#1435934-00-1 (dihydrochloride)

Theoretical Analysis

MedKoo Cat#: 598524

Name: LDN-193189 HCl

CAS#: 1435934-00-1 (dihydrochloride)

Chemical Formula: C25H24Cl2N6

Exact Mass: 0.0000

Molecular Weight: 479.41

Elemental Analysis: C, 62.63; H, 5.05; Cl, 14.79; N, 17.53

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,450.00	2 Weeks
1g	USD 3,650.00	2 Weeks
2g	USD 5,650.00	2 Weeks

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Related CAS #

1062368-24-4 (free base) 1062368-62-0 (HCl) 1435934-00-1 (dihydrochloride)

Synonym

LDN-193189 monohydrochloride; LDN-193189 HCl; LDN193189; LDN-193189; LDN 193189; LDN193189; DM-3189; DM 3189; DM3189;

IUPAC/Chemical Name

4-(6-(4-(piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline dihydrochloride

InChi Key

CMQXLLAILGGLRV-UHFFFAOYSA-N

InChi Code

InChI=1S/C25H22N6.2ClH/c1-2-4-24-22(3-1)21(9-10-27-24)23-16-29-31-17-19(15-28-25(23)31)18-5-7-20(8-6-18)30-13-11-26-12-14-30;;/h1-10,15-17,26H,11-14H2;2*1H

SMILES Code

[H]Cl.[H]Cl.C1(C2=C3N=CC(C4=CC=C(N5CCNCC5)C=C4)=CN3N=C2)=CC=NC6=CC=CC=C16

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

>3 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

Instruction

View handling instruction

Biological target:

LDN193189 is a potent selective BMP type I receptor (BMP I) inhibitor.

In vitro activity:

LDN193189 inhibits BMP4-mediated Smad1, Smad5 and Smad8 activation with greater potency than did dorsomorphin (IC50=5 nM versus 470 nM) while retaining 200-fold selectivity for BMP signaling versus TGF-β signaling (IC50 for TGF-β ≥1,000 nM). LDN193189 efficiently inhibits transcriptional activity of the BMP type I receptors ALK2 and ALK3 (IC50=5 nM and 30 nM, respectively), and the TGF-β type I receptors ALK4, ALK5 and ALK7 (IC50≥500 nM) and increases selectivity for BMP signaling versus AMP-activated protein kinase, PDGFR and MAPK signaling pathways as compared to the parent compound. LDN-193189 blocks the transcriptional activity induced by either constitutively active ALK2R206H or ALK2Q207D mutant proteins. These findings suggest that LDN193189 might affect BMP-induced osteoblast differentiation. In fact, LDN193189 inhibits the induction of alkaline phosphatase activity in C2C12 cells by BMP4 even when administered 12 h after BMP stimulation, indicating sustained BMP signaling activity is needed for osteogenic differentiation. Reference: Nat Med. 2008 Dec;14(12):1363-9. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19029982/

In vivo activity:

In the present study, the aim was to investigate the impact of the LDN-193189 compound, a potent inhibitor of the BMP type I receptor, on metastasis development in vivo. ZNF217-revLuc cells were injected into the left ventricle of nude mice (n = 16) while control mice (n = 13) were inoculated with control pcDNA6-revLuc cells. Mice from each group were treated or not with LDN-193189 for 35 days. We found that systemic LDN-193189 treatment of mice significantly enhanced metastasis development, by increasing both the number and the size of metastases. In pcDNA6-revLuc-injected mice, LDN-193189 also affected the kinetics of metastasis emergence. Altogether, these data suggest that in vivo, LDN-193189 might affect the interaction between breast cancer cells and the bone environment, favoring the emergence and development of multiple metastases. Hence, our report highlights the importance of the choice of drugs and therapeutic strategies used in the management of bone metastases. Reference: Front Pharmacol. 2019 Jun 19;10:667. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31275146/

	Solvent	mg/mL	mM
Solubility
	DMF	1.0	2.09
	DMSO	5.8	12.09

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 479.41 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. Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Kamiya N, Fukuda T, Mishina Y, Peterson RT, Bloch KD. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 2008 Dec;14(12):1363-9. doi: 10.1038/nm.1888. Epub 2008 Nov 30. Erratum in: Nat Med. 2009 Jan;15(1):117. PMID: 19029982; PMCID: PMC2846458. 2. Lee YC, Cheng CJ, Bilen MA, Lu JF, Satcher RL, Yu-Lee LY, Gallick GE, Maity SN, Lin SH. BMP4 promotes prostate tumor growth in bone through osteogenesis. Cancer Res. 2011 Aug 1;71(15):5194-203. doi: 10.1158/0008-5472.CAN-10-4374. Epub 2011 Jun 13. PMID: 21670081; PMCID: PMC3148283. 3. Vollaire J, Machuca-Gayet I, Lavaud J, Bellanger A, Bouazza L, El Moghrabi S, Treilleux I, Coll JL, Peyruchaud O, Josserand V, Cohen PA. The Bone Morphogenetic Protein Signaling Inhibitor LDN-193189 Enhances Metastasis Development in Mice. Front Pharmacol. 2019 Jun 19;10:667. doi: 10.3389/fphar.2019.00667. PMID: 31275146; PMCID: PMC6593094.

In vitro protocol:

In vivo protocol:

1. Lee YC, Cheng CJ, Bilen MA, Lu JF, Satcher RL, Yu-Lee LY, Gallick GE, Maity SN, Lin SH. BMP4 promotes prostate tumor growth in bone through osteogenesis. Cancer Res. 2011 Aug 1;71(15):5194-203. doi: 10.1158/0008-5472.CAN-10-4374. Epub 2011 Jun 13. PMID: 21670081; PMCID: PMC3148283. 2. Vollaire J, Machuca-Gayet I, Lavaud J, Bellanger A, Bouazza L, El Moghrabi S, Treilleux I, Coll JL, Peyruchaud O, Josserand V, Cohen PA. The Bone Morphogenetic Protein Signaling Inhibitor LDN-193189 Enhances Metastasis Development in Mice. Front Pharmacol. 2019 Jun 19;10:667. doi: 10.3389/fphar.2019.00667. PMID: 31275146; PMCID: PMC6593094.

1: Horbelt D, Boergermann JH, Chaikuad A, Alfano I, Williams E, Lukonin I, Timmel T, Bullock AN, Knaus P. Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation. J Biol Chem. 2015 Feb 6;290(6):3390-404. doi: 10.1074/jbc.M114.604397. Epub 2014 Nov 3. PubMed PMID: 25368322; PubMed Central PMCID: PMC4319009. 2: Ali JL, Lagasse BJ, Minuk AJ, Love AJ, Moraya AI, Lam L, Arthur G, Gibson SB, Morrison LC, Werbowetski-Ogilvie TE, Fu Y, Nachtigal MW. Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells. Int J Cancer. 2015 Mar 1;136(5):E455-69. doi: 10.1002/ijc.29220. Epub 2014 Sep 26. PubMed PMID: 25227893. 3: Boergermann JH, Kopf J, Yu PB, Knaus P. Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells. Int J Biochem Cell Biol. 2010 Nov;42(11):1802-7. doi: 10.1016/j.biocel.2010.07.018. Epub 2010 Aug 5. PubMed PMID: 20691279. 4: Derwall M, Malhotra R, Lai CS, Beppu Y, Aikawa E, Seehra JS, Zapol WM, Bloch KD, Yu PB. Inhibition of bone morphogenetic protein signaling reduces vascular calcification and atherosclerosis. Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):613-22. doi: 10.1161/ATVBAHA.111.242594. Epub 2012 Jan 5. PubMed PMID: 22223731; PubMed Central PMCID: PMC3679546. 5: Malhotra R, Burke MF, Martyn T, Shakartzi HR, Thayer TE, O'Rourke C, Li P, Derwall M, Spagnolli E, Kolodziej SA, Hoeft K, Mayeur C, Jiramongkolchai P, Kumar R, Buys ES, Yu PB, Bloch KD, Bloch DB. Inhibition of bone morphogenetic protein signal transduction prevents the medial vascular calcification associated with matrix Gla protein deficiency. PLoS One. 2015 Jan 20;10(1):e0117098. doi: 10.1371/journal.pone.0117098. eCollection 2015. PubMed PMID: 25603410; PubMed Central PMCID: PMC4300181. 6: Lai Y, Xie C, Zhang S, Gan G, Wu D, Chen W. Bone morphogenetic protein type I receptor inhibition induces cleft palate associated with micrognathia and cleft lower lip in mice. Birth Defects Res A Clin Mol Teratol. 2016 Jul;106(7):612-23. doi: 10.1002/bdra.23504. Epub 2016 May 6. PubMed PMID: 27150428. 7: Vogt J, Traynor R, Sapkota GP. The specificities of small molecule inhibitors of the TGFß and BMP pathways. Cell Signal. 2011 Nov;23(11):1831-42. doi: 10.1016/j.cellsig.2011.06.019. Epub 2011 Jun 29. PubMed PMID: 21740966. 8: Sanvitale CE, Kerr G, Chaikuad A, Ramel MC, Mohedas AH, Reichert S, Wang Y, Triffitt JT, Cuny GD, Yu PB, Hill CS, Bullock AN. A new class of small molecule inhibitor of BMP signaling. PLoS One. 2013 Apr 30;8(4):e62721. doi: 10.1371/journal.pone.0062721. Print 2013. PubMed PMID: 23646137; PubMed Central PMCID: PMC3639963. 9: Yamasaki A, Kasai A, Toi A, Kurita M, Kimoto S, Hayata-Takano A, Nakazawa T, Nagayasu K, Shintani N, Hashimoto R, Ito A, Meltzer HY, Ago Y, Waschek JA, Onaka Y, Matsuda T, Baba A, Hashimoto H. Identification of the role of bone morphogenetic protein (BMP) and transforming growth factor-β (TGF-β) signaling in the trajectory of serotonergic differentiation in a rapid assay in mouse embryonic stem cells in vitro. J Neurochem. 2015 Feb;132(4):418-28. doi: 10.1111/jnc.12999. Epub 2015 Jan 23. PubMed PMID: 25421849. 10: Theurl M, Nairz M, Schroll A, Sonnweber T, Asshoff M, Haschka D, Seifert M, Willenbacher W, Wilflingseder D, Posch W, Murphy AT, Witcher DR, Theurl I, Weiss G. Hepcidin as a predictive factor and therapeutic target in erythropoiesis-stimulating agent treatment for anemia of chronic disease in rats. Haematologica. 2014 Sep;99(9):1516-24. doi: 10.3324/haematol.2013.099481. Epub 2014 Jun 3. PubMed PMID: 24895335; PubMed Central PMCID: PMC4562542. 11: Ahsan S, Ge Y, Tainsky MA. Combinatorial therapeutic targeting of BMP2 and MEK-ERK pathways in NF1-associated malignant peripheral nerve sheath tumors. Oncotarget. 2016 Aug 30;7(35):57171-57185. doi: 10.18632/oncotarget.11036. PubMed PMID: 27494873; PubMed Central PMCID: PMC5302981. 12: Steinbicker AU, Sachidanandan C, Vonner AJ, Yusuf RZ, Deng DY, Lai CS, Rauwerdink KM, Winn JC, Saez B, Cook CM, Szekely BA, Roy CN, Seehra JS, Cuny GD, Scadden DT, Peterson RT, Bloch KD, Yu PB. Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. Blood. 2011 May 5;117(18):4915-23. doi: 10.1182/blood-2010-10-313064. Epub 2011 Mar 10. PubMed PMID: 21393479; PubMed Central PMCID: PMC3100698. 13: Zeng H, Ortiz A, Shen PF, Cheng CJ, Lee YC, Yu G, Lin SC, Creighton CJ, Yu-Lee LY, Lin SH. Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway. Oncotarget. 2017 Feb 7;8(6):10145-10160. doi: 10.18632/oncotarget.14358. PubMed PMID: 28052036; PubMed Central PMCID: PMC5354648. 14: Tadokoro T, Gao X, Hong CC, Hotten D, Hogan BL. BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors. Development. 2016 Mar 1;143(5):764-73. doi: 10.1242/dev.126656. Epub 2016 Jan 25. PubMed PMID: 26811382; PubMed Central PMCID: PMC4813333. 15: Gomez-Stallons MV, Wirrig-Schwendeman EE, Hassel KR, Conway SJ, Yutzey KE. Bone Morphogenetic Protein Signaling Is Required for Aortic Valve Calcification. Arterioscler Thromb Vasc Biol. 2016 Jul;36(7):1398-405. doi: 10.1161/ATVBAHA.116.307526. Epub 2016 May 19. PubMed PMID: 27199449; PubMed Central PMCID: PMC4919184. 16: Shahid M, Spagnolli E, Ernande L, Thoonen R, Kolodziej SA, Leyton PA, Cheng J, Tainsh RE, Mayeur C, Rhee DK, Wu MX, Scherrer-Crosbie M, Buys ES, Zapol WM, Bloch KD, Bloch DB. BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2016 Apr 15;310(8):H984-94. doi: 10.1152/ajpheart.00879.2015. Epub 2016 Feb 12. PubMed PMID: 26873969; PubMed Central PMCID: PMC4867336. 17: Kanamori Y, Murakami M, Matsui T, Funaba M. The regulation of hepcidin expression by serum treatment: requirements of the BMP response element and STAT- and AP-1-binding sites. Gene. 2014 Nov 10;551(2):119-26. doi: 10.1016/j.gene.2014.08.037. Epub 2014 Aug 21. PubMed PMID: 25151311. 18: Sun CC, Vaja V, Chen S, Theurl I, Stepanek A, Brown DE, Cappellini MD, Weiss G, Hong CC, Lin HY, Babitt JL. A hepcidin lowering agent mobilizes iron for incorporation into red blood cells in an adenine-induced kidney disease model of anemia in rats. Nephrol Dial Transplant. 2013 Jul;28(7):1733-43. doi: 10.1093/ndt/gfs584. Epub 2013 Jan 22. PubMed PMID: 23345622; PubMed Central PMCID: PMC3707526. 19: Nahar-Gohad P, Gohad N, Tsai CC, Bordia R, Vyavahare N. Rat aortic smooth muscle cells cultured on hydroxyapatite differentiate into osteoblast-like cells via BMP-2-SMAD-5 pathway. Calcif Tissue Int. 2015 Apr;96(4):359-69. doi: 10.1007/s00223-015-9962-z. Epub 2015 Mar 1. PubMed PMID: 25725805; PubMed Central PMCID: PMC4393885. 20: Cook BD, Evans T. BMP signaling balances murine myeloid potential through SMAD-independent p38MAPK and NOTCH pathways. Blood. 2014 Jul 17;124(3):393-402. doi: 10.1182/blood-2014-02-556993. Epub 2014 Jun 3. PubMed PMID: 24894772; PubMed Central PMCID: PMC4102711.