NPASS Compound

Natural Product: NPC199277

Natural Product ID	NPC199277
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-Methoxy-9H-Carbazol-3-Ol
IUPAC Name	2-methoxy-9H-carbazol-3-ol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2037028
PubChem CID	15182256
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0000210] Carbazoles

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 27 29 0 0 0 0 0 0 0 0999 V2000 4.4304 0.8909 0.4080 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7824 -0.3412 0.1693 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4032 -0.3955 0.0876 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6263 0.7338 0.2342 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2475 0.7046 0.1567 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3492 -0.5122 -0.0768 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4272 -1.6668 -0.2276 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8005 -1.6037 -0.1448 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5966 -2.7240 -0.2889 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7063 -0.2962 -0.1124 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7597 -1.1602 -0.3114 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0438 -0.6684 -0.2974 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2912 0.6687 -0.0884 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2339 1.5284 0.1101 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9401 1.0618 0.1007 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7367 1.6329 0.2590 N 0 0 0 0 0 0 0 0 0 0 0 0 4.0260 1.6453 -0.2926 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2072 1.1817 1.4645 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5283 0.7781 0.2828 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1136 1.6783 0.4167 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0318 -2.6248 -0.4109 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7436 -3.2120 -1.1676 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6145 -2.2298 -0.4814 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8721 -1.3496 -0.4542 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3212 1.0538 -0.0787 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4480 2.5745 0.2725 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5843 2.6516 0.4362 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 6 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 8 3 1 0 15 10 1 0 16 5 1 0 1 17 1 0 1 18 1 0 1 19 1 0 4 20 1 0 7 21 1 0 9 22 1 0 11 23 1 0 12 24 1 0 13 25 1 0 14 26 1 0 16 27 1 0 M END

Standard InCHIKey	KDLDZUFUKYBJCQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C13H11NO2/c1-16-13-7-11-9(6-12(13)15)8-4-2-3-5-10(8)14-11/h2-7,14-15H,1H3
SMILES	COc1cc2c(cc1O)c1ccccc1[nH]2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	213.08	Volume:	220.493 ? Van der Waals volume.
Dense:	0.966	LogP:	3.077 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.761 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.243 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	15.0
TPSA:	45.25 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.652	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.909	Fsp³:	0.077
MCE-18:	15.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.418	Fluc inhibitor:	0.607 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.975 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.478 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.141	Promiscuous compounds:	0.882

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.94	MDCK Permeability:	-4.735
Pgp-inhibitor:	0.04	Pgp-substrate:	0.295
PAMPA:	0.387 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.031
20% Bioavailability (F20%):	0.187	30% Bioavailability (F30%):	0.375
50% Bioavailability (F50%):	0.923

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.059	MRP1:	0.741
Plasma Protein Binding (PPB):	98.079%	Volume Distribution (VD):	0.112
Fu:	2.064% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.985
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.909
BSEP inhibitor:	0.78

ADMET: Metabolism

CYP1A2-inhibitor:	0.965	CYP1A2-substrate:	0.218
CYP2C19-inhibitor:	0.379	CYP2C19-substrate:	0.024
CYP2C9-inhibitor:	0.996	CYP2C9-substrate:	0.49
CYP2D6-inhibitor:	0.975	CYP2D6-substrate:	0.194
CYP3A4-inhibitor:	0.032	CYP3A4-substrate:	0.479
CYP2B6-substrate:	0.008	CYP2C8-inhibitor:	0.998
HLM stability:	0.564 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

4.337

Half-life (T1/2):

1.537

ADMET: Toxicity

hERG Blockers:	0.219	hERG Blockers (10um):	0.627
Human Hepatotoxicity (H-HT):	0.598	Drug-induced Liver Injury (DILI):	0.727
AMES Toxicity:	0.767	Rat Oral Acute Toxicity:	0.591
Maximum Recommended Daily Dose:	0.647	Skin Sensitization:	0.731
Carcinogencity:	0.71	Eye Corrosion:	0.014
Eye Irritation:	0.98	Respiratory Toxicity:	0.939
Drug-induced Neurotoxicity:	0.637	Ototoxicity:	0.397
Hematotoxicity:	0.449	Drug-induced Nephrotoxicity:	0.659
Genotoxicity:	0.59	RPMI-8226 Immunitoxicity:	0.123
A549 Cytotoxicity:	0.393	Hek293 Cytotoxicity:	0.599
BCF:	1.125 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.709 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.761 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.256 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO28993	Streptomyces venezuelae	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11720530]
NPO28993	Streptomyces venezuelae	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[16724858]
NPO29161	Hyptis urticoides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19265396]
NPO28993	Streptomyces venezuelae	Species	Streptomycetaceae	Bacteria	n.a.	Guam Island, Pacific Ocean	n.a.	PMID[21774474]
NPO28993	Streptomyces venezuelae	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[22050382]
NPO4806	Clausena wallichii	Species	Rutaceae	Eukaryota	Roots	n.a.	n.a.	PMID[22482432]
NPO28993	Streptomyces venezuelae	Species	Streptomycetaceae	Bacteria	n.a.	Guam Island, Pacific Ocean	n.a.	PMID[23164710]
NPO28993	Streptomyces venezuelae	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[26203536]
NPO24890	Iris sanguinea	Species	Iridaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[28951079]
NPO24890	Iris sanguinea	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28993	Streptomyces venezuelae	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29161	Hyptis urticoides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29073	Ipomoea carnea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29028	Cicer cuneatum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28961	Croton hutchinsonianus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28943	Daldinia vernicosa	Species	Xylariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29461	Sarcophyton infundibuliforme	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29035	Pseudomonas cichorii	Species	Pseudomonadaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24890	Iris sanguinea	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24890	Iris sanguinea	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28500	Griselinia scandens	Species	Griseliniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23710	Otholobium pubescens	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4806	Clausena wallichii	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29070	Bulbine asphodeloides	Species	Asphodelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28993	Streptomyces venezuelae	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO28544	Podocalyx loranthoides	Species	Picrodendraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24890	Iris sanguinea	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25073	Saccharina latissima	Species	Laminariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29497	Delphinium speciosum	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28427	Gutenbergia marginata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27349	Rhododendron edgeworthii	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25248	Gloydius blomhoffii	Species	Viperidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29073	Ipomoea carnea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29518	Nardia scalaris	Species	Solenostomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29180	Monachosorum maximowiczii	Species	Dennstaedtiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28961	Croton hutchinsonianus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29095	Yucca elata	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29161	Hyptis urticoides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29321	Octopus octopodia	Species	Octopodidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29028	Cicer cuneatum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27603	Populus candicans	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28735	Helicia erratica	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29461	Sarcophyton infundibuliforme	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29387	Eudendrium racemosum	Species	Eudendriidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28639	Trixis grisebachii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29035	Pseudomonas cichorii	Species	Pseudomonadaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO28943	Daldinia vernicosa	Species	Xylariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
MIC	2
IC50	3

Activity Type	# Activity
Cell line	3
Organism	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell line	KB	Homo sapiens	IC50	=	213000.0	nM	PMID[22482432]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	31400.0	nM	PMID[22482432]
NPT639	Cell line	NCI-H187	Homo sapiens	IC50	=	27400.0	nM	PMID[22482432]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	MIC	=	128.0	ug.mL-1	PMID[22482432]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	128.0	ug.mL-1	PMID[22482432]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC199277 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	30963
0.1-0.2	17107
0.2-0.3	1596
0.3-0.4	165
0.4-0.5	21
0.5-0.6	3
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7045	Intermediate Similarity	NPC135887
0.5625	Remote Similarity	NPC607426
0.54	Remote Similarity	NPC308137
0.5192	Remote Similarity	NPC116238

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC199277 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5680
0.1-0.2	3380
0.2-0.3	83
0.3-0.4	7
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data