Alectinib HCl | AF 802 | CH5424802 | RO5424802 | CAS#1256580-46-7 | 1256589-74-8 | ALK inhibitor

MedKoo Cat#: 206629 | Name: Alectinib HCl

Description:

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

Alectinib, also known as AF802, or CH5424802 or RO5424802, is a potent, selective, and orally available ALK inhibitor with a unique chemical scaffold, showing preferential antitumor activity against cancers with gene alterations of ALK, such as nonsmall cell lung cancer (NSCLC) cells expressing EML4-ALK fusion and anaplastic large-cell lymphoma (ALCL) cells expressing NPM-ALK fusion in vitro and in vivo. Alectinib inhibited ALK L1196M, which corresponds to the gatekeeper mutation conferring common resistance to kinase inhibitors, and blocked EML4-ALK L1196M-driven cell growth. Alectinib (as HCl salt) was approved in Dec. 2015.

Chemical Structure

Alectinib HCl

CAS#1256589-74-8 (HCl)

Theoretical Analysis

MedKoo Cat#: 206629

Name: Alectinib HCl

CAS#: 1256589-74-8 (HCl)

Chemical Formula: C30H35ClN4O2

Exact Mass: 0.0000

Molecular Weight: 519.09

Elemental Analysis: C, 69.42; H, 6.80; Cl, 6.83; N, 10.79; O, 6.16

Price and Availability

Size	Price	Availability
25mg	USD 90.00	Ready to ship
50mg	USD 150.00	Ready to ship
100mg	USD 225.00	Ready to ship
250mg	USD 450.00	Ready to ship
500mg	USD 750.00	Ready to ship
1g	USD 1,250.00	Ready to ship

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Related CAS #

1256580-46-7 (free base) 1256589-74-8 (HCl)

Synonym

AF 802; AF-802; AF802; CH5424802; CH5424802; CH 5424802; RO5424802; RO 5424802; RO5424802, Alectinib; brand name: Alecensa

IUPAC/Chemical Name

9-ethyl-6,6-dimethyl-8-(4-morpholin-4-ylpiperidin-1-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile;hydrochloride

InChi Key

GYABBVHSRIHYJR-UHFFFAOYSA-N

InChi Code

InChI=1S/C30H34N4O2.ClH/c1-4-20-16-23-24(17-26(20)34-9-7-21(8-10-34)33-11-13-36-14-12-33)30(2,3)29-27(28(23)35)22-6-5-19(18-31)15-25(22)32-29;/h5-6,15-17,21,32H,4,7-14H2,1-3H3;1H

SMILES Code

N#CC1=CC2=C(C=C1)C3=C(C(C)(C)C4=CC(N5CCC(N6CCOCC6)CC5)=C(CC)C=C4C3=O)N2.[H]Cl

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

Related CAS# CAS#1256580-46-7 (Alectinib free base) CAS#1256589-74-8 (Alectinib HCl)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC60815

QC Data

View QC data: current batch, Lot#TZC60815

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Alectinib Hydrochloride (CH5424802 Hydrochloride; RO5424802 Hydrochloride; AF-802 Hydrochloride) is an ALK inhibitor with an IC50 of 1.9 nM and a Kd value of 2.4 nM (in an ATP-competitive manner), and also inhibits ALK F1174L and ALK R1275Q with IC50s of 1 nM and 3.5 nM, respectively.

In vitro activity:

This study selected six NB cell lines, including three ALK-WT cell lines (IMR-32, NB-19, and SK-N-AS) and three ALK-mutant cell lines (Kelly, SH-SY5Y, and LA-N-6). The results show that cell viability was greatly reduced by alectinib treatment in all six cell lines tested (Figure 1A), and there were morphological changes in the NB cells (Figure 1C). The IC50s of the cell lines tested ranges from 3.181 μM to 9.6 μM. ALK mutated cells Kelly and SH-SY5Y were relatively more sensitive to the treatment of alectinib and showed greater inhibition of cell growth. In addition, alectinib showed potent inhibitory effects on ALK-WT cells (Figure 1B) with IC50s ranging from 4 to 9.4 μM. These results indicated that alectinib significantly inhibits cell growth in both ALK-WT and ALK-mutant NB cells. Reference: Cancer Lett. 2017 Aug 1; 400: 61–68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502736/

In vivo activity:

EHMES-10 cells developed pleural carcinomatosis accompanied by thoracic tumors and malignant pleural effusions within 28 days after intrathoracic (orthotopic) inoculation (Figure 4A). Alectinib treatment given from day 15 to day 28 remarkably inhibited the production of thoracic tumors and pleural effusions as determined by CT scans on day 28 (Figure 4A). Accordingly, the weight of thoracic tumors and the volume of pleural effusions in alectinib-treated mice were significantly lower than those of control mice (Figure 4B, 4C). To further assess whether alectinib rescued pleural carcinomatosis, an in vivo imaging model was utilized. For this model, luciferase-transfected EHMES-10 cells (EHMES-10/Eluc) were established. Elevated bioluminescence was detected in mice inoculated with EHMES-10/Eluc cells by day 24, indicating the presence of pleural carcinomatosis. Bioluminescence in control mice consistently increased over the course of the experiment, but bioluminescence in alectinib-treated mice decreased. These results clearly indicated that alectinib treatment rescued the pleural carcinomatosis produced by EHMES-10/Eluc cells (Figure 5A, 5B). Reference: Oncotarget. 2017 Sep 26; 8(43): 73766–73773. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650298/

	Solvent	mg/mL	mM
Solubility
	DMSO	3.5	6.74

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 519.09 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. Arai S, Kita K, Tanimoto A, Takeuchi S, Fukuda K, Sato H, Yano S. In vitro and in vivo anti-tumor activity of alectinib in tumor cells with NCOA4-RET. Oncotarget. 2017 May 16;8(43):73766-73773. doi: 10.18632/oncotarget.17900. PMID: 29088743; PMCID: PMC5650298. 2. Lu J, Guan S, Zhao Y, Yu Y, Woodfield SE, Zhang H, Yang KL, Bieerkehazhi S, Qi L, Li X, Gu J, Xu X, Jin J, Muscal JA, Yang T, Xu GT, Yang J. The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model. Cancer Lett. 2017 Aug 1;400:61-68. doi: 10.1016/j.canlet.2017.04.022. Epub 2017 Apr 26. PMID: 28455243; PMCID: PMC5502736.

In vitro protocol:

In vivo protocol:

1: Ou SH, Weitz M, Jalas JR, Kelly DF, Wong V, Azada MC, Quines O, Klempner SJ. Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation. Lung Cancer. 2016 Jun;96:15-8. doi: 10.1016/j.lungcan.2016.03.008. Epub 2016 Mar 26. PubMed PMID: 27133743. 2: Tchekmedyian N, Ali SM, Miller VA, Haura EB. Acquired ALK L1152R Mutation Confers Resistance to Ceritinib and Predicts Response to Alectinib. J Thorac Oncol. 2016 Apr 15. pii: S1556-0864(16)30081-8. doi: 10.1016/j.jtho.2016.03.018. [Epub ahead of print] PubMed PMID: 27091190. 3: Aikawa H, Hayashi M, Ryu S, Yamashita M, Ohtsuka N, Nishidate M, Fujiwara Y, Hamada A. Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging. Sci Rep. 2016 Mar 30;6:23749. doi: 10.1038/srep23749. PubMed PMID: 27026287; PubMed Central PMCID: PMC4812395. 4: Dong X, Fernandez-Salas E, Li E, Wang S. Elucidation of Resistance Mechanisms to Second-Generation ALK Inhibitors Alectinib and Ceritinib in Non-Small Cell Lung Cancer Cells. Neoplasia. 2016 Mar;18(3):162-71. doi: 10.1016/j.neo.2016.02.001. PubMed PMID: 26992917; PubMed Central PMCID: PMC4796802. 5: Tanaka H, Taima K, Morimoto T, Nakamura K, Tanaka Y, Itoga M, Takanashi S, Okumura K. Dramatic response to alectinib in a patient of ALK-rearranged lung cancer with poor performance status. BMC Res Notes. 2016 Mar 17;9(1):173. doi: 10.1186/s13104-016-1983-9. PubMed PMID: 26987388; PubMed Central PMCID: PMC4794901. 6: Yoshida T, Hida T, Yatabe Y. Rapid and dramatic response to alectinib in an ALK rearranged non-small-cell lung cancer patient who are critically ill. Anticancer Drugs. 2016 Mar 2. [Epub ahead of print] PubMed PMID: 26938871. 7: Yoshimura Y, Kurasawa M, Yorozu K, Puig O, Bordogna W, Harada N. Antitumor activity of alectinib, a selective ALK inhibitor, in an ALK-positive NSCLC cell line harboring G1269A mutation : Efficacy of alectinib against ALK G1269A mutated cells. Cancer Chemother Pharmacol. 2016 Mar;77(3):623-8. doi: 10.1007/s00280-016-2977-y. Epub 2016 Feb 5. PubMed PMID: 26849637. 8: Gainor JF, Chi AS, Logan J, Hu R, Oh KS, Brastianos PK, Shih HA, Shaw AT. Alectinib Dose Escalation Reinduces Central Nervous System Responses in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Relapsing on Standard Dose Alectinib. J Thorac Oncol. 2016 Feb;11(2):256-60. doi: 10.1016/j.jtho.2015.10.010. Epub 2015 Dec 18. PubMed PMID: 26845119; PubMed Central PMCID: PMC4743545. 9: Takegawa N, Hayashi H, Iizuka N, Takahama T, Ueda H, Tanaka K, Takeda M, Nakagawa K. Transformation of ALK rearrangement-positive adenocarcinoma to small-cell lung cancer in association with acquired resistance to alectinib. Ann Oncol. 2016 May;27(5):953-5. doi: 10.1093/annonc/mdw032. Epub 2016 Jan 24. PubMed PMID: 26811347. 10: Pirker R, Filipits M. Alectinib in RET-rearranged non-small cell lung cancer-Another progress in precision medicine? Transl Lung Cancer Res. 2015 Dec;4(6):797-800. doi: 10.3978/j.issn.2218-6751.2015.03.08. PubMed PMID: 26798590; PubMed Central PMCID: PMC4700226. 11: Fujita S, Masago K, Katakami N, Yatabe Y. Transformation to SCLC after Treatment with the ALK Inhibitor Alectinib. J Thorac Oncol. 2016 Jan 2. pii: S1556-0864(15)00275-0. doi: 10.1016/j.jtho.2015.12.105. [Epub ahead of print] PubMed PMID: 26751586. 12: Alectinib Approved for ALK+ Lung Cancer. Cancer Discov. 2016 Feb;6(2):115. doi: 10.1158/2159-8290.CD-NB2016-001. Epub 2016 Jan 6. PubMed PMID: 26739884. 13: Isozaki H, Ichihara E, Takigawa N, Ohashi K, Ochi N, Yasugi M, Ninomiya T, Yamane H, Hotta K, Sakai K, Matsumoto K, Hosokawa S, Bessho A, Sendo T, Tanimoto M, Kiura K. Non-Small Cell Lung Cancer Cells Acquire Resistance to the ALK Inhibitor Alectinib by Activating Alternative Receptor Tyrosine Kinases. Cancer Res. 2016 Mar 15;76(6):1506-16. doi: 10.1158/0008-5472.CAN-15-1010. Epub 2015 Dec 30. PubMed PMID: 26719536. 14: Shaw AT, Gandhi L, Gadgeel S, Riely GJ, Cetnar J, West H, Camidge DR, Socinski MA, Chiappori A, Mekhail T, Chao BH, Borghaei H, Gold KA, Zeaiter A, Bordogna W, Balas B, Puig O, Henschel V, Ou SH; study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016 Feb;17(2):234-42. doi: 10.1016/S1470-2045(15)00488-X. Epub 2015 Dec 19. PubMed PMID: 26708155; PubMed Central PMCID: PMC4752892. 15: Jassem J. Alectinib in crizotinib-resistant, ALK-positive NSCLC. Lancet Oncol. 2016 Feb;17(2):134-5. doi: 10.1016/S1470-2045(15)00555-0. Epub 2015 Dec 19. PubMed PMID: 26708154. 16: Tani T, Yasuda H, Hamamoto J, Kuroda A, Arai D, Ishioka K, Ohgino K, Miyawaki M, Kawada I, Naoki K, Hayashi Y, Betsuyaku T, Soejima K. Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells. Mol Cancer Ther. 2016 Jan;15(1):162-71. doi: 10.1158/1535-7163.MCT-15-0084. Epub 2015 Dec 18. PubMed PMID: 26682573. 17: Miyamoto S, Ikushima S, Ono R, Awano N, Kondo K, Furuhata Y, Fukumoto K, Kumasaka T. Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib. Jpn J Clin Oncol. 2016 Feb;46(2):170-3. doi: 10.1093/jjco/hyv173. Epub 2015 Nov 27. PubMed PMID: 26613679. 18: Ou SH, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, Lena H, Moro-Sibilot D, Bearz A, Ramirez SV, Mekhail T, Spira A, Bordogna W, Balas B, Morcos PN, Monnet A, Zeaiter A, Kim DW. Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study. J Clin Oncol. 2016 Mar 1;34(7):661-8. doi: 10.1200/JCO.2015.63.9443. Epub 2015 Nov 23. PubMed PMID: 26598747. 19: Song Z, Wang M, Zhang A. Alectinib: a novel second generation anaplastic lymphoma kinase (ALK) inhibitor for overcoming clinically-acquired resistance. Acta Pharm Sin B. 2015 Jan;5(1):34-7. doi: 10.1016/j.apsb.2014.12.007. Epub 2015 Jan 24. Review. PubMed PMID: 26579422; PubMed Central PMCID: PMC4629211. 20: Takeuchi K, Togashi Y, Kamihara Y, Fukuyama T, Yoshioka H, Inoue A, Katsuki H, Kiura K, Nakagawa K, Seto T, Maemondo M, Hida T, Harada M, Ohe Y, Nogami N, Yamamoto N, Nishio M, Tamura T. Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study). Ann Oncol. 2016 Jan;27(1):185-92. doi: 10.1093/annonc/mdv501. Epub 2015 Oct 20. PubMed PMID: 26487585; PubMed Central PMCID: PMC4684157.