This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Ambroxol	The risk or severity of methemoglobinemia can be increased when 7-Hydroxystaurosporine is combined with Ambroxol.
Articaine	The risk or severity of methemoglobinemia can be increased when 7-Hydroxystaurosporine is combined with Articaine.
Benzocaine	The risk or severity of methemoglobinemia can be increased when 7-Hydroxystaurosporine is combined with Benzocaine.
Benzyl alcohol	The risk or severity of methemoglobinemia can be increased when 7-Hydroxystaurosporine is combined with Benzyl alcohol.
Bupivacaine	The risk or severity of methemoglobinemia can be increased when 7-Hydroxystaurosporine is combined with Bupivacaine.

Food Interactions

Not Available

Chemical Identifiers

UNII: 7BU5H4V94A
CAS number: 112953-11-4
InChI Key: PBCZSGKMGDDXIJ-HQCWYSJUSA-N
InChI: InChI=1S/C28H26N4O4/c1-28-25(35-3)15(29-2)12-18(36-28)31-16-10-6-4-8-13(16)19-21-22(27(34)30-26(21)33)20-14-9-5-7-11-17(14)32(28)24(20)23(19)31/h4-11,15,18,25,27,29,34H,12H2,1-3H3,(H,30,33)/t15-,18-,25-,27-,28+/m1/s1
IUPAC Name: (2S,3R,4R,6R,18R)-18-hydroxy-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.1^{2,6}.0^{7,28}.0^{8,13}.0^{15,19}.0^{20,27}.0^{21,26}]nonacosa-8(13),9,11,14,19,21(26),22,24,27-nonaen-16-one
SMILES: [H][C@]12C[C@@H](NC)[C@@H](OC)[C@](C)(O1)N1C3=C(C=CC=C3)C3=C4[C@@H](O)NC(=O)C4=C4C5=C(C=CC=C5)N2C4=C13

References

General References

Not Available

External Links

PubChem Compound: 72271
PubChem Substance: 46508077
ChemSpider: 65225
BindingDB: 17054
ChEMBL: CHEMBL1236539
ZINC: ZINC000003814435
Therapeutic Targets Database: DCL001064
PDBe Ligand: UCN

PDB Entries

1nvq / 1okz / 1pkd / 7oub

Clinical Trials

Clinical Trials Clinical Trial & Rare Diseases Add-on Data Package Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package

Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
Unlock 175K+ rows when you subscribe.View sample data
2	Completed	Treatment	Extensive-stage Small Cell Lung Cancer (SCLC) / Recurrent Small Cell Lung Cancer (SCLC)	1	somestatus	stop reason	just information to hide
2	Completed	Treatment	Fallopian Tube Cancer / Ovarian Cancer / Primary Peritoneal Cancer	1	somestatus	stop reason	just information to hide
2	Completed	Treatment	Pancreatic Cancer	1	somestatus	stop reason	just information to hide
2	Terminated	Treatment	Lymphoma, Large-Cell, Ki-1 / T-Cell Lymphoma	1	somestatus	stop reason	just information to hide
2	Terminated	Treatment	Recurrent Melanoma / Stage IV Melanoma	1	somestatus	stop reason	just information to hide

Pharmacoeconomics

Manufacturers: Not Available
Packagers: Not Available
Dosage Forms: Not Available
Prices: Not Available
Patents: Not Available

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0789 mg/mL	ALOGPS
logP	2.42	ALOGPS
logP	3.41	Chemaxon
logS	-3.8	ALOGPS
pKa (Strongest Acidic)	10.8	Chemaxon
pKa (Strongest Basic)	9.52	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	5	Chemaxon
Hydrogen Donor Count	3	Chemaxon
Polar Surface Area	89.68 Å²	Chemaxon
Rotatable Bond Count	2	Chemaxon
Refractivity	133.4 m³·mol^-1	Chemaxon
Polarizability	51.47 Å³	Chemaxon
Number of Rings	8	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.608
Blood Brain Barrier	-	0.9237
Caco-2 permeable	-	0.5545
P-glycoprotein substrate	Substrate	0.6904
P-glycoprotein inhibitor I	Non-inhibitor	0.6076
P-glycoprotein inhibitor II	Non-inhibitor	0.7074
Renal organic cation transporter	Non-inhibitor	0.8762
CYP450 2C9 substrate	Non-substrate	0.7188
CYP450 2D6 substrate	Non-substrate	0.8225
CYP450 3A4 substrate	Substrate	0.71
CYP450 1A2 substrate	Non-inhibitor	0.7904
CYP450 2C9 inhibitor	Non-inhibitor	0.8677
CYP450 2D6 inhibitor	Non-inhibitor	0.8983
CYP450 2C19 inhibitor	Non-inhibitor	0.825
CYP450 3A4 inhibitor	Non-inhibitor	0.7542
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.7792
Ames test	Non AMES toxic	0.6281
Carcinogenicity	Non-carcinogens	0.8714
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.5979 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9993
hERG inhibition (predictor II)	Non-inhibitor	0.8151

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-001i-0000900000-18b450ef69f1e5d63655
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-001i-0000900000-87ee37b60f8523946c51
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-001i-0001900000-b387605b1219929de0a6
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-001i-2000900000-6b92af3f7d7a53014e5c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-000t-0109600000-b86d324b9e1e5698df7c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0f6x-5203900000-d5dd1576980966e0a24a
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	215.9646105	predicted	DarkChem Lite v0.1.0
[M-H]-	215.5201105	predicted	DarkChem Lite v0.1.0
[M-H]-	225.8851	predicted	DeepCCS 1.0 (2019)
[M+H]+	215.7916105	predicted	DarkChem Lite v0.1.0
[M+H]+	217.1379105	predicted	DarkChem Lite v0.1.0
[M+H]+	227.78052	predicted	DeepCCS 1.0 (2019)
[M+Na]+	214.9836105	predicted	DarkChem Lite v0.1.0
[M+Na]+	217.0530105	predicted	DarkChem Lite v0.1.0
[M+Na]+	233.55852	predicted	DeepCCS 1.0 (2019)

Targets

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Details1. Serine/threonine-protein kinase Chk1

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14559997, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:19734889, PubMed:20090422, PubMed:9278511). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758)
Specific Function: Atp binding
Gene Name: CHEK1
Uniprot ID: O14757
Uniprot Name: Serine/threonine-protein kinase Chk1
Molecular Weight: 54433.115 Da

References

Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	5	7.5	30	A29761
IC 50 (nM)	6	7.5	30	A29762

Details2. 3-phosphoinositide-dependent protein kinase 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive
Specific Function: 3-phosphoinositide-dependent protein kinase activity
Gene Name: PDPK1
Uniprot ID: O15530
Uniprot Name: 3-phosphoinositide-dependent protein kinase 1
Molecular Weight: 63151.305 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]

Drug created at June 13, 2005 13:24 / Updated at August 26, 2024 19:23

7-Hydroxystaurosporine

Identification

Structure for 7-Hydroxystaurosporine (DB01933)

Pharmacology

Interactions

Categories

Chemical Identifiers

References

Clinical Trials

Clinical Trial & Rare Diseases Add-on Data Package

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References