HA-15 free base
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MedKoo CAT#: 406823

CAS#: 1609402-14-3

Description: HA15 is a specifc inhibitor of the chaperone BiP (Binding immunoglobulin protein, GRP78 or HSPA5). HA15 displayed anti-cancerous activity on all melanoma cells tested, including cells isolated from patients and cells that developed resistance to BRAF inhibitors. HA15 also exhibited strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors. Transcriptomic, proteomic, and biochemical studies identified the chaperone BiP/GRP78/HSPA5 as the specific target of HA15 and demonstrated that the interaction increases ER stress, leading to melanoma cell death by concomitant induction of autophagic and apoptotic mechanisms.


Chemical Structure

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HA-15 free base
CAS# 1609402-14-3

Theoretical Analysis

MedKoo Cat#: 406823
Name: HA-15 free base
CAS#: 1609402-14-3
Chemical Formula: C23H22N4O3S2
Exact Mass: 466.11
Molecular Weight: 466.574
Elemental Analysis: C, 59.21; H, 4.75; N, 12.01; O, 10.29; S, 13.74

Price and Availability

Size Price Availability Quantity
10mg USD 110 Ready to ship
25mg USD 245 Ready to ship
50mg USD 425 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 4250 Ready to ship
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Synonym: HA15; HA-15; HA 15.

IUPAC/Chemical Name: N-(4-(3-((5-(dimethylamino)naphthalene)-1-sulfonamido)phenyl)thiazol-2-yl)acetamide

InChi Key: LBSMEKVVMYSTIH-UHFFFAOYSA-N

InChi Code: InChI=1S/C23H22N4O3S2/c1-15(28)24-23-25-20(14-31-23)16-7-4-8-17(13-16)26-32(29,30)22-12-6-9-18-19(22)10-5-11-21(18)27(2)3/h4-14,26H,1-3H3,(H,24,25,28)

SMILES Code: CC(NC1=NC(C2=CC=CC(NS(=O)(C3=C4C=CC=C(N(C)C)C4=CC=C3)=O)=C2)=CS1)=O

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:

Biological target: HA15 is an inhibitor of ER chaperone BiP/GRP78/HSPA5, and inhibits the ATPase activity of BiP.
In vitro activity: Both VEEV TrD and EEEV infectious viral titers were significantly impacted by HA15 treatment with a 3 log10 reduction observed in cells treated with 50 µM of HA15 (Figure 3A,B). HA15 treatment of SINV infected Vero cells at 50 µM and 25 µM reduced the viral titers from 2.18 × 107 PFU/mL (DMSO treated cells) to 1.00 × 104 PFU/mL and 1.43 × 106 PFU/mL, respectively (Figure 3C). Likewise, HA15 treatment impacted CHIKV infectious viral titers, reducing them from 4.4 × 107 PFU/mL (DMSO treated cells) to 3.33 × 104 PFU/mL (HA15 50 µM) and 3.13 × 106 PFU/mL (HA15 25µM) (Figure 3D). These results agree with the data demonstrating the ability of HA15 to inhibit VEEV TC-83 infectious titers (Figure 2E), indicating that HA15 inhibition of GRP78 impacts multiple alphaviruses. Reference: Pathogens. 2021 Mar; 10(3): 283. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000471/
In vivo activity: Another interesting finding was that HA15-induced apoptosis was maintained at a high level in LPS-treated cells, regardless of whether or not β-arrestin-2 was overexpressed (Figure 5D). In this study’s animal models, KO+NEC and WT+NEC mice pretreated with HA15 exhibited almost the same degree of intestinal damage (Figure 5E), further confirming the involvement of BiP in β-arrestin-2-induced ER stress and apoptotic signaling. Reference: Aging (Albany NY). 2019 Oct 15; 11(19): 8294–8312. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814604/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 71.5 153.24
Ethanol 45.0 96.45

Preparing Stock Solutions

The following data is based on the product molecular weight 466.57 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. Barrera MD, Callahan V, Akhrymuk I, Bhalla N, Zhou W, Campbell C, Narayanan A, Kehn-Hall K. Proteomic Discovery of VEEV E2-Host Partner Interactions Identifies GRP78 Inhibitor HA15 as a Potential Therapeutic for Alphavirus Infections. Pathogens. 2021 Mar 2;10(3):283. doi: 10.3390/pathogens10030283. PMID: 33801554; PMCID: PMC8000471. 2. Wu J, Wu Y, Lian X. Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy. Biol Open. 2020 Nov 12;9(11):bio053298. doi: 10.1242/bio.053298. PMID: 33115703; PMCID: PMC7673357. 3. Fu D, Li P, Sheng Q, Lv Z. β-arrestin-2 enhances intestinal epithelial apoptosis in necrotizing enterocolitis. Aging (Albany NY). 2019 Oct 14;11(19):8294-8312. doi: 10.18632/aging.102320. Epub 2019 Oct 14. PMID: 31612867; PMCID: PMC6814604. 4. Xu D, Yang H, Yang Z, Berezowska S, Gao Y, Liang SQ, Marti TM, Hall SRR, Dorn P, Kocher GJ, Schmid RA, Peng RW. Endoplasmic Reticulum Stress Signaling as a Therapeutic Target in Malignant Pleural Mesothelioma. Cancers (Basel). 2019 Oct 8;11(10):1502. doi: 10.3390/cancers11101502. PMID: 31597321; PMCID: PMC6827154.
In vitro protocol: 1. Barrera MD, Callahan V, Akhrymuk I, Bhalla N, Zhou W, Campbell C, Narayanan A, Kehn-Hall K. Proteomic Discovery of VEEV E2-Host Partner Interactions Identifies GRP78 Inhibitor HA15 as a Potential Therapeutic for Alphavirus Infections. Pathogens. 2021 Mar 2;10(3):283. doi: 10.3390/pathogens10030283. PMID: 33801554; PMCID: PMC8000471. 2. Wu J, Wu Y, Lian X. Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy. Biol Open. 2020 Nov 12;9(11):bio053298. doi: 10.1242/bio.053298. PMID: 33115703; PMCID: PMC7673357.
In vivo protocol: 1. Fu D, Li P, Sheng Q, Lv Z. β-arrestin-2 enhances intestinal epithelial apoptosis in necrotizing enterocolitis. Aging (Albany NY). 2019 Oct 14;11(19):8294-8312. doi: 10.18632/aging.102320. Epub 2019 Oct 14. PMID: 31612867; PMCID: PMC6814604. 2. Xu D, Yang H, Yang Z, Berezowska S, Gao Y, Liang SQ, Marti TM, Hall SRR, Dorn P, Kocher GJ, Schmid RA, Peng RW. Endoplasmic Reticulum Stress Signaling as a Therapeutic Target in Malignant Pleural Mesothelioma. Cancers (Basel). 2019 Oct 8;11(10):1502. doi: 10.3390/cancers11101502. PMID: 31597321; PMCID: PMC6827154.

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1. Compounds Triggering ER Stress Exert Anti-​Melanoma Effects and Overcome BRAF Inhibitor Resistance
By Cerezo, Michael; Lehraiki, Abdelali; Millet, Antoine; Rouaud, Florian; Plaisant, Magali; Jaune, Emilie; Botton, Thomas; Ronco, Cyril; Abbe, Patricia; Amdouni, Hella; et al. From Cancer Cell (2016), 29(6), 805-819. | Language: English, Database: CAPLUS

2. Preparation of arylsulfonamido thiazole derivs. as antitumor agents
By Rocchi, Stephane; Ballotti, Robert; Benhida, Rachid; Cerezo, Michael; Duca, Maria; Joly, Jean-Patrick
From PCT Int. Appl. (2014), WO 2014072486 A1 20140515. | Language: English, Database: CAPLUS