NPASS Compound

Natural Product: NPC475269

Natural Product ID	NPC475269
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Xanthene-9-Thione
IUPAC Name	xanthene-9-thione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL502408
PubChem CID	300362
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans [CHEMONTID:0002817] Dibenzopyrans [CHEMONTID:0000200] Xanthenes

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 23 25 0 0 0 0 0 0 0 0999 V2000 -0.2682 2.8602 -0.4365 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.1375 1.2550 -0.1948 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2245 0.4119 -0.0907 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4859 0.9618 -0.1976 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5865 0.1394 -0.0969 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4771 -1.2135 0.1068 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2098 -1.7388 0.2101 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0878 -0.9441 0.1140 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1260 -1.4261 0.2098 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1922 -0.6694 0.1182 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1191 0.6909 -0.0859 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2657 1.4860 -0.1816 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5230 0.9301 -0.0739 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6097 -0.4285 0.1302 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4761 -1.2051 0.2235 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5732 2.0284 -0.3583 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5505 0.5993 -0.1846 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3723 -1.8145 0.1785 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0774 -2.7990 0.3707 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1545 2.5502 -0.3423 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4300 1.5029 -0.1412 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5839 -0.8969 0.2193 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5706 -2.2800 0.3855 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 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 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 11 2 1 0 8 3 1 0 15 10 1 0 4 16 1 0 5 17 1 0 6 18 1 0 7 19 1 0 12 20 1 0 13 21 1 0 14 22 1 0 15 23 1 0 M END

Standard InCHIKey	VKLOKHJKPPJQMM-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C13H8OS/c15-13-9-5-1-3-7-11(9)14-12-8-4-2-6-10(12)13/h1-8H
SMILES	S=c1c2ccccc2oc2c1cccc2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	212.03	Volume:	216.579 ? Van der Waals volume.
Dense:	0.979	LogP:	3.514 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.326 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.849 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	17.0
TPSA:	13.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.407	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.064	Fsp³:	0.0
MCE-18:	14.0 ? 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:	1
Colloidal aggregators:	0.421	Fluc inhibitor:	0.827 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.32 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.39 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.926	Promiscuous compounds:	0.43

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.655	MDCK Permeability:	-4.629
Pgp-inhibitor:	0.936	Pgp-substrate:	0.021
PAMPA:	0.142 ? 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):	0.01
20% Bioavailability (F20%):	0.218	30% Bioavailability (F30%):	0.596
50% Bioavailability (F50%):	0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.153	MRP1:	0.65
Plasma Protein Binding (PPB):	97.635%	Volume Distribution (VD):	-0.115
Fu:	1.27% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.779
OATP1B3 inhibitor:	0.992	BCRP inhibitor:	0.591
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.992	CYP1A2-substrate:	0.98
CYP2C19-inhibitor:	0.468	CYP2C19-substrate:	0.957
CYP2C9-inhibitor:	0.296	CYP2C9-substrate:	0.937
CYP2D6-inhibitor:	0.153	CYP2D6-substrate:	0.523
CYP3A4-inhibitor:	0.063	CYP3A4-substrate:	0.949
CYP2B6-substrate:	0.617	CYP2C8-inhibitor:	0.632
HLM stability:	0.976 ? 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):

3.45

Half-life (T1/2):

0.991

ADMET: Toxicity

hERG Blockers:	0.032	hERG Blockers (10um):	0.702
Human Hepatotoxicity (H-HT):	0.473	Drug-induced Liver Injury (DILI):	0.998
AMES Toxicity:	0.618	Rat Oral Acute Toxicity:	0.682
Maximum Recommended Daily Dose:	0.556	Skin Sensitization:	0.96
Carcinogencity:	0.941	Eye Corrosion:	0.159
Eye Irritation:	0.976	Respiratory Toxicity:	0.821
Drug-induced Neurotoxicity:	0.117	Ototoxicity:	0.038
Hematotoxicity:	0.181	Drug-induced Nephrotoxicity:	0.006
Genotoxicity:	0.551	RPMI-8226 Immunitoxicity:	0.031
A549 Cytotoxicity:	0.108	Hek293 Cytotoxicity:	0.417
BCF:	2.365 ? 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:	4.507 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.52 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.247 ? 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
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18464091]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18558747]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	stem bark	Pangradin village, Jasinga, West Java, Indonesia	2005-AUG	PMID[19839614]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20817450]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	n.a.	pericarp	n.a.	PMID[24555285]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24717154]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	fruit hulls	Madras, Tamil Nadu, India	1993-MAR	PMID[9213587]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6249	Garcinia mangostana	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6249	Garcinia mangostana	Species	Clusiaceae	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
Inhibition	12

Activity Type	# Activity
Organism	12

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
NPT2647	Organism	Drechslera	Drechslera	Inhibition	=	11.0	%	Open TG-GATES in vivo data: Hematology
NPT2647	Organism	Drechslera	Drechslera	Inhibition	=	5.0	%	PMID[25442304]
NPT2647	Organism	Drechslera	Drechslera	Inhibition	=	-11.0	%	PMID[22264895]
NPT2647	Organism	Drechslera	Drechslera	Inhibition	=	10.0	%	PMID[11784156]
NPT2648	Organism	Fusarium oxysporum f. sp. vasinfectum	Fusarium oxysporum f. sp. vasinfectum	Inhibition	=	2.0	%	PMID[20020916]
NPT2648	Organism	Fusarium oxysporum f. sp. vasinfectum	Fusarium oxysporum f. sp. vasinfectum	Inhibition	=	4.0	%	PMID[19506060]
NPT2648	Organism	Fusarium oxysporum f. sp. vasinfectum	Fusarium oxysporum f. sp. vasinfectum	Inhibition	=	6.0	%	DOI[10.6019/CHEMBL1201861]
NPT2646	Organism	Alternaria tenuis	Alternaria tenuis	Inhibition	=	-6.0	%	PMID[24571273]
NPT2646	Organism	Alternaria tenuis	Alternaria tenuis	Inhibition	=	-12.0	%	PMID[20738102]
NPT2646	Organism	Alternaria tenuis	Alternaria tenuis	Inhibition	=	-22.0	%	PMID[19035792]
NPT2646	Organism	Alternaria tenuis	Alternaria tenuis	Inhibition	=	-32.0	%	PMID[22276679]

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 NPC475269 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	42295
0.1-0.2	6642
0.2-0.3	780
0.3-0.4	105
0.4-0.5	16
0.5-0.6	11
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC35744
0.6857	Remote Similarity	NPC278787
0.6857	Remote Similarity	NPC601623
0.6486	Remote Similarity	NPC605893
0.6389	Remote Similarity	NPC602252
0.6389	Remote Similarity	NPC606736
0.6316	Remote Similarity	NPC231013
0.6053	Remote Similarity	NPC600210
0.5897	Remote Similarity	NPC239495
0.5854	Remote Similarity	NPC292214
0.575	Remote Similarity	NPC608827
0.5476	Remote Similarity	NPC200221
0.5476	Remote Similarity	NPC17055
0.5476	Remote Similarity	NPC610896
0.5357	Remote Similarity	NPC246214
0.5349	Remote Similarity	NPC608745
0.5294	Remote Similarity	NPC279916
0.5227	Remote Similarity	NPC271779
0.5227	Remote Similarity	NPC88645

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475269 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7038
0.1-0.2	1988
0.2-0.3	111
0.3-0.4	11
0.4-0.5	2
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