ATIPRIMOD

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H44N2
Molecular Weight	336.5982
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC1(CCC)CCC2(CCN(CCCN(CC)CC)C2)CC1

InChI

InChIKey=SERHTTSLBVGRBY-UHFFFAOYSA-N

InChI=1S/C22H44N2/c1-5-10-21(11-6-2)12-14-22(15-13-21)16-19-24(20-22)18-9-17-23(7-3)8-4/h5-20H2,1-4H3

HIDE SMILES / InChI

Molecular Formula	C22H44N2
Molecular Weight	336.5982
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15970928

Atiprimod is an oral azaspirane which was initially developed by Smith Kline and French Laboratories for treating rheumatoid arthritis (discontinued in phase I). Due to its anti-inflammatory, antineoplastic, and antiangiogenic properties, the drug was tested in patients with Neuroendocrine Carcinoma and Multiple Myeloma and reached phase II (discontinued). In vitro studies revealed that atiprimod exerts its action by inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3), blocking the signalling pathways of interleukin-6 and vascular endothelial growth factor (VEGF) and downregulating the anti-apoptotic proteins Bcl-2, Bcl-XL, and Mcl-1, thereby inhibiting cell proliferation, inducing cell cycle arrest, and inducing apoptosis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Jak-STAT signaling pathway 9 Target ID: map04630 Sources: www.ncbi.nlm.nih.gov/pubmed/20372971	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Neuroendocrine carcinoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00388063	Primary		Phase II 1132	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://clinicaltrials.gov/ct2/show/NCT00086216	Primary		Phase II 1132	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
BOC Sciences	123018-47-3	http://www.bocsci.com/description.asp?cas=123018-47-3
Compound Cloud	129869
Compound Cloud	166556
Compound Cloud	9808089
MolPort	MolPort-035-765-766	https://www.molport.com/shop/molecule-link/MolPort-035-765-766
Molnova	M10907	https://www.molnova.com/en/serch-list.html?keywords=M10907
Molnova	M11208	https://www.molnova.com/en/serch-list.html?keywords=M11208
MuseChem	I003148	https://www.musechem.com/product/I003148.html
MuseChem	I010985	https://www.musechem.com/product/I010985.html
MuseChem	I012809	https://www.musechem.com/product/I012809.html
Tocris	4580	https://www.tocris.com/search.php?Type=QuickSearch&Value=4580
eMolecules	110070918	https://orderbb.emolecules.com/search/#?query=110070918

PubMed

Title	Date	PubMed
Atiprimod is an inhibitor of cancer cell proliferation and angiogenesis.	2004 Dec	15844657
Atiprimod blocks STAT3 phosphorylation and induces apoptosis in multiple myeloma cells.	2005 Jul 11	15970928
A clinically relevant SCID-hu in vivo model of human multiple myeloma.	2005 Jul 15	15817674
Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo.	2005 Jun 1	15705788
Biological pathways and in vivo antitumor activity induced by Atiprimod in myeloma.	2007 Dec	17882285
Deactivation of Akt and STAT3 signaling promotes apoptosis, inhibits proliferation, and enhances the sensitivity of hepatocellular carcinoma cells to an anticancer agent, Atiprimod.	2007 Jan	17237271
Atiprimod: a multi-functional drug candidate for myeloid and other malignancies.	2007 Jan	16860863
Atiprimod blocks phosphorylation of JAK-STAT and inhibits proliferation of acute myeloid leukemia (AML) cells.	2007 Jan	16828865
Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways.	2007 Jun 15	17317853
A severe combined immunodeficient-hu in vivo mouse model of human primary mantle cell lymphoma.	2008 Apr 1	18381957
New developments in the pathology of malignant lymphoma: a review of the literature published from May to July 2008.	2008 Sep	19669214
Advances in the treatment of gastroenteropancreatic neuroendocrine tumors.	2010	21694850

Sample Use Guides

In Vivo Use Guide

Neuroendocrine Carcinoma: Atiprimod is administered orally as a single daily dose of 120 mg/day for 14 days, followed by a 14-day treatment-free period. Multiple Myeloma: atiprimod was given at ten dose levels - 30, 60, 90, 120, 180, 240, 300, 360, 420, and 480 mg/day or 180, 240, 300, 360, 420, and 480 mg/day (in combination with ursodiol).

Route of Administration: Oral

In Vitro Use Guide

U266-B1 cells were incubated with 8 uM atiprimod to measure how the drug suppresses IL-6 production. Atiprimod attenuated IL6 supernatant levels to 23, 42, 53, and 130 pg/ml at 1, 6, 8, and 16 hours, respectively. NF-kB activity in the same cell line was blocked after 4 h of incubation with 50 uM atiprimod and after 24 h when using 8 uM of the drug. The percentage of cells undergoing apoptotic cell death also increased from 10.89 to 46.27% after exposure to 8 uM atiprimod.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:15:30 GMT 2023` Edited by `admin` on `Fri Dec 15 16:15:30 GMT 2023`
Record UNII	MG7D3QD743
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ATIPRIMOD

Official Name

English

SKF-106615

Code

English

ATIPRIMOD [MART.]

Common Name

English

SK&F-106615

Code

English

2-(3-(DIETHYLAMINO)PROPYL)-8,8-DIPROPYL-2-AZASPIRO(4.5)DECANE

Systematic Name

English

2-AZASPIRO(4.5)DECANE-2-PROPANAMINE N,N-DIETHYL-8,8-DIPROPYL-

Common Name

English

atiprimod [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C274