NPASS Compound

Natural Product: NPC118228

Natural Product ID	NPC118228
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Clausine E
IUPAC Name	methyl 1-hydroxy-9H-carbazole-3-carboxylate
Synonyms	Clausine E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL235934
PubChem CID	5315951
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 29 31 0 0 0 0 0 0 0 0999 V2000 5.4566 -0.7897 -0.6703 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2169 -0.3160 -0.1775 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9931 -0.6421 -0.6954 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9654 -1.4209 -1.6833 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7265 -0.1358 -0.1638 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5279 -0.5062 -0.7357 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6484 0.0005 -0.1956 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9747 -0.1805 -0.5388 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6131 -0.9126 -1.5202 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9968 -0.8854 -1.6048 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7506 -0.1348 -0.7198 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0671 0.5760 0.2384 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6948 0.5730 0.3528 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8531 1.1985 1.2167 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.6073 0.8613 0.8971 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5890 1.2355 1.4737 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7379 0.7193 0.9192 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6837 2.0876 2.5600 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3657 -1.8961 -0.7640 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7697 -0.3003 -1.6031 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2004 -0.5946 0.1565 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4929 -1.1827 -1.5947 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0509 -1.5141 -2.2330 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4746 -1.4663 -2.3811 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8275 -0.1376 -0.8160 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6155 1.1756 0.9500 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1272 1.8352 1.9988 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6936 1.0138 1.3742 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8823 1.7395 3.4911 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 3 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 17 5 1 0 15 7 2 0 13 8 1 0 1 19 1 0 1 20 1 0 1 21 1 0 6 22 1 0 9 23 1 0 10 24 1 0 11 25 1 0 12 26 1 0 14 27 1 0 17 28 1 0 18 29 1 0 M END

Standard InCHIKey	ZWPODTIRGFOENJ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C14H11NO3/c1-18-14(17)8-6-10-9-4-2-3-5-11(9)15-13(10)12(16)7-8/h2-7,15-16H,1H3
SMILES	COC(=O)c1cc2c3ccccc3[nH]c2c(c1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	241.07	Volume:	243.943 ? Van der Waals volume.
Dense:	0.988	LogP:	3.468 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.156 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.729 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	16.0
TPSA:	62.32 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.644	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.031	Fsp³:	0.071
MCE-18:	16.0 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.291	Fluc inhibitor:	0.461 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.964 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.426 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.095	Promiscuous compounds:	0.6

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.316	MDCK Permeability:	-4.749
Pgp-inhibitor:	0.048	Pgp-substrate:	0.076
PAMPA:	0.715 ? 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):	0.004
20% Bioavailability (F20%):	0.37	30% Bioavailability (F30%):	0.528
50% Bioavailability (F50%):	0.92

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019	MRP1:	1.0
Plasma Protein Binding (PPB):	98.022%	Volume Distribution (VD):	-0.07
Fu:	1.556% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.802
OATP1B3 inhibitor:	0.981	BCRP inhibitor:	0.533
BSEP inhibitor:	0.818

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.993
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.992
CYP2C9-inhibitor:	0.134	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.432	CYP2D6-substrate:	0.016
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.028
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.995 ? 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):

5.509

Half-life (T1/2):

0.952

ADMET: Toxicity

hERG Blockers:	0.151	hERG Blockers (10um):	0.625
Human Hepatotoxicity (H-HT):	0.358	Drug-induced Liver Injury (DILI):	0.859
AMES Toxicity:	0.707	Rat Oral Acute Toxicity:	0.558
Maximum Recommended Daily Dose:	0.716	Skin Sensitization:	0.49
Carcinogencity:	0.668	Eye Corrosion:	0.002
Eye Irritation:	0.971	Respiratory Toxicity:	0.82
Drug-induced Neurotoxicity:	0.697	Ototoxicity:	0.439
Hematotoxicity:	0.189	Drug-induced Nephrotoxicity:	0.586
Genotoxicity:	0.608	RPMI-8226 Immunitoxicity:	0.125
A549 Cytotoxicity:	0.33	Hek293 Cytotoxicity:	0.452
BCF:	1.042 ? 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:	3.887 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.835 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.47 ? 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
NPO29109	Clausena anisata	Species	Rutaceae	Eukaryota	n.a.	seed	n.a.	DOI[10.1080/10412905.1999.9701119]
NPO29109	Clausena anisata	Species	Rutaceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1080/10412905.1999.9701119]
NPO29109	Clausena anisata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10650093]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11000023]
NPO21978	Clausena harmandiana	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO29109	Clausena anisata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19459693]
NPO21978	Clausena harmandiana	Species	Rutaceae	Eukaryota	n.a.	root	n.a.	PMID[21302964]
NPO18135	Clausena vestita	Species	Rutaceae	Eukaryota	whole plants	Yunnan Province, China	2008-JAN	PMID[22093759]
NPO29109	Clausena anisata	Species	Rutaceae	Eukaryota	leaf oil	n.a.	n.a.	PMID[22472691]
NPO21978	Clausena harmandiana	Species	Rutaceae	Eukaryota	Root barks	n.a.	n.a.	PMID[3236015]
NPO21978	Clausena harmandiana	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29109	Clausena anisata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29109	Clausena anisata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29109	Clausena anisata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29109	Clausena anisata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO19266	Clausena excavata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21978	Clausena harmandiana	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18135	Clausena vestita	Species	Rutaceae	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
IC50	14
Activity	20

Activity Type	# Activity
Individual protein	1
Cell line	27
Non-molecular	2
Others	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1510	Individual protein	Alpha-ketoglutarate-dependent dioxygenase FTO	Homo sapiens	IC50	=	27790.0	nM	PMID[34792334]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	600.0	nM	PMID[17548198]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	1900.0	nM	PMID[17548198]
NPT2338	Cell line	SW48	Homo sapiens	IC50	=	21000.0	nM	PMID[17548198]
NPT660	Cell line	SW480	Homo sapiens	IC50	=	4800.0	nM	PMID[17548198]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	60.0	%	PMID[17548198]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	12.1	%	PMID[17548198]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	28.0	%	PMID[17548198]
NPT2338	Cell line	SW48	Homo sapiens	Activity	=	65.6	%	PMID[17548198]
NPT2338	Cell line	SW48	Homo sapiens	Activity	=	12.5	%	PMID[17548198]
NPT2338	Cell line	SW48	Homo sapiens	Activity	=	21.9	%	PMID[17548198]
NPT660	Cell line	SW480	Homo sapiens	Activity	=	59.9	%	PMID[17548198]
NPT660	Cell line	SW480	Homo sapiens	Activity	=	17.5	%	PMID[17548198]
NPT660	Cell line	SW480	Homo sapiens	Activity	=	25.7	%	PMID[17548198]
NPT80	Cell line	Raji	Homo sapiens	Activity	=	60.0	%	PMID[10650093]
NPT80	Cell line	Raji	Homo sapiens	Activity	>	80.0	%	PMID[10650093]
NPT639	Cell line	NCI-H187	Homo sapiens	IC50	=	94590.0	nM	PMID[21302964]
NPT91	Cell line	KB	Homo sapiens	IC50	=	107560.0	nM	PMID[21302964]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	152050.0	nM	PMID[21302964]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	15800.0	nM	PMID[22093759]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	13300.0	nM	PMID[22093759]
NPT1125	Cell line	T98G	Homo sapiens	IC50	=	71600.0	nM	PMID[22093759]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	37100.0	nM	PMID[22093759]
NPT65	Cell line	HepG2	Homo sapiens	Activity	=	55.9	%	PMID[22093759]
NPT65	Cell line	HepG2	Homo sapiens	Activity	=	31.1	%	PMID[22093759]
NPT65	Cell line	HepG2	Homo sapiens	Activity	=	13.1	%	PMID[22093759]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	35000.0	nM	PMID[17548198]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	16900.0	nM	PMID[22093759]
NPT2	Others	Unspecified	n.a.	Activity	=	27.4	%	PMID[10650093]
NPT2	Others	Unspecified	n.a.	Activity	=	42.4	%	PMID[10650093]
NPT2	Others	Unspecified	n.a.	Activity	=	74.6	%	PMID[10650093]
NPT2	Others	Unspecified	n.a.	Activity	=	100.0	%	PMID[10650093]

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 NPC118228 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	26361
0.1-0.2	21915
0.2-0.3	1398
0.3-0.4	150
0.4-0.5	25
0.5-0.6	5
0.6-0.7	2
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
0.6735	Remote Similarity	NPC283117
0.6327	Remote Similarity	NPC160381
0.5741	Remote Similarity	NPC3207
0.5636	Remote Similarity	NPC39500
0.5484	Remote Similarity	NPC51388
0.5357	Remote Similarity	NPC39679
0.5094	Remote Similarity	NPC611466

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC118228 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5170
0.1-0.2	3862
0.2-0.3	115
0.3-0.4	3
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