NPASS Compound

Natural Product: NPC202157

Natural Product ID	NPC202157
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Anomalin A
IUPAC Name	2,3,6,8-tetrahydroxy-1-methylxanthen-9-one
Synonyms	Anomalin A
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL454440
PubChem CID	10423452
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans [CHEMONTID:0002817] Dibenzopyrans [CHEMONTID:0000200] Xanthenes [CHEMONTID:0000204] Xanthones

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 30 32 0 0 0 0 0 0 0 0999 V2000 -5.3613 1.1470 0.0711 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0720 0.5990 0.0732 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8797 -0.7674 0.1045 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6078 -1.3005 0.1064 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3909 -2.6691 0.1374 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4998 -0.4663 0.0768 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6651 0.9033 0.0453 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9485 1.3985 0.0444 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6055 1.6946 0.0171 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6084 1.2053 0.0185 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8625 -0.1655 0.0493 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2287 -1.0017 0.0788 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0435 -2.2314 0.1067 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1500 -0.6577 0.0501 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4090 -2.1120 0.0828 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2037 0.2381 0.0195 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9573 1.5894 -0.0109 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6786 2.0831 -0.0118 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0647 2.4451 -0.0410 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5129 -0.2336 0.0196 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5243 1.9502 -0.5220 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7322 -1.4224 0.1275 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0567 -3.0877 0.9861 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0877 2.4791 0.0196 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0550 -2.6489 -0.8164 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0676 -2.5915 1.0255 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5268 -2.2814 0.0840 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5195 3.1527 -0.0362 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1455 3.1179 -0.7917 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9421 -0.3662 0.9355 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 4 6 2 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 11 14 1 0 14 15 1 0 14 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 16 20 1 0 8 2 1 0 18 10 1 0 12 6 1 0 1 21 1 0 3 22 1 0 5 23 1 0 8 24 1 0 15 25 1 0 15 26 1 0 15 27 1 0 18 28 1 0 19 29 1 0 20 30 1 0 M END

Standard InCHIKey	YPBXGIBBOZOVPM-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C14H10O6/c1-5-11-10(4-8(17)13(5)18)20-9-3-6(15)2-7(16)12(9)14(11)19/h2-4,15-18H,1H3
SMILES	Oc1cc(O)c2c(c1)oc1c(c2=O)c(C)c(c(c1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	274.05	Volume:	259.317 ? Van der Waals volume.
Dense:	1.057	LogP:	1.377 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.65 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.895 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	17.0
TPSA:	111.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.369	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.701	Fsp³:	0.071
MCE-18:	19.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.832	Fluc inhibitor:	0.645 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.899 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.326 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.504	Promiscuous compounds:	0.528

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.629	MDCK Permeability:	-4.852
Pgp-inhibitor:	0.067	Pgp-substrate:	0.782
PAMPA:	0.36 ? 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):	0.024
20% Bioavailability (F20%):	0.393	30% Bioavailability (F30%):	0.912
50% Bioavailability (F50%):	0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.033	MRP1:	0.862
Plasma Protein Binding (PPB):	96.739%	Volume Distribution (VD):	-0.633
Fu:	2.588% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.636
OATP1B3 inhibitor:	0.867	BCRP inhibitor:	0.97
BSEP inhibitor:	0.717

ADMET: Metabolism

CYP1A2-inhibitor:	0.998	CYP1A2-substrate:	0.011
CYP2C19-inhibitor:	0.008	CYP2C19-substrate:	0.046
CYP2C9-inhibitor:	0.721	CYP2C9-substrate:	0.027
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.012
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.941 ? 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):

5.896

Half-life (T1/2):

1.456

ADMET: Toxicity

hERG Blockers:	0.055	hERG Blockers (10um):	0.641
Human Hepatotoxicity (H-HT):	0.369	Drug-induced Liver Injury (DILI):	0.834
AMES Toxicity:	0.728	Rat Oral Acute Toxicity:	0.562
Maximum Recommended Daily Dose:	0.87	Skin Sensitization:	0.972
Carcinogencity:	0.768	Eye Corrosion:	0.833
Eye Irritation:	0.999	Respiratory Toxicity:	0.84
Drug-induced Neurotoxicity:	0.004	Ototoxicity:	0.186
Hematotoxicity:	0.027	Drug-induced Nephrotoxicity:	0.004
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.013
A549 Cytotoxicity:	0.642	Hek293 Cytotoxicity:	0.611
BCF:	1.189 ? 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:	3.879 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.691 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.229 ? 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
NPO6427	Wardomyces anomalus	Species	Microascaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1021/np020518b]
NPO6427	Wardomyces anomalus	Species	Microascaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12762814]
NPO33500	Arthrinium sp.	Species	Apiosporaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16246554]
NPO33500	Arthrinium sp.	Species	Apiosporaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21741249]
NPO33500	Arthrinium sp.	Species	Apiosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6427	Wardomyces anomalus	Species	Microascaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6427	Wardomyces anomalus	Species	Microascaceae	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
Activity	6
IC50	20
Inhibition	2
IZ	1

Activity Type	# Activity
Individual protein	18
Cell line	4
Others	4
Organism	1
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT13	Individual protein	Tyrosine-protein kinase LCK	Homo sapiens	Activity	=	0.0	%	PMID[19258276]
NPT1661	Individual protein	ALK tyrosine kinase receptor	Homo sapiens	IC50	=	1100.0	nM	PMID[22418278]
NPT1660	Individual protein	NUAK family SNF1-like kinase 1	Homo sapiens	IC50	=	15600.0	nM	Open TG-GATES in vivo data: Biochemistry
NPT1433	Individual protein	Serine/threonine-protein kinase Aurora-B	Homo sapiens	IC50	=	500.0	nM	Open TG-GATES in vivo data: Biochemistry
NPT1659	Individual protein	Tyrosine-protein kinase receptor UFO	Homo sapiens	IC50	=	6600.0	nM	Open TG-GATES in vivo data: Biochemistry
NPT1436	Individual protein	Focal adhesion kinase 1	Homo sapiens	IC50	=	15200.0	nM	PMID[23484668]
NPT1438	Individual protein	Insulin-like growth factor I receptor	Homo sapiens	IC50	=	8600.0	nM	PMID[23200246]
NPT1337	Individual protein	Hepatocyte growth factor receptor	Homo sapiens	IC50	=	4400.0	nM	PMID[25304895]
NPT1658	Individual protein	Serine/threonine-protein kinase NEK2	Homo sapiens	IC50	=	83900.0	nM	PMID[25849312]
NPT1657	Individual protein	Serine/threonine-protein kinase NEK6	Homo sapiens	IC50	=	67800.0	nM	PMID[23910596]
NPT1265	Individual protein	Serine/threonine-protein kinase PIM1	Homo sapiens	IC50	=	300.0	nM	Open TG-GATES in vivo data: Hematology
NPT1656	Individual protein	Protein kinase N1	Homo sapiens	IC50	=	45300.0	nM	PMID[21070010]
NPT1478	Individual protein	Vascular endothelial growth factor receptor 2	Homo sapiens	IC50	=	800.0	nM	PMID[19326880]
NPT491	Individual protein	Dual specificity mitogen-activated protein kinase kinase 1	Homo sapiens	IC50	>	100000.0	nM	PMID[25707013]
NPT831	Individual protein	Serine/threonine-protein kinase PLK1	Homo sapiens	IC50	=	8800.0	nM	PMID[20155932]
NPT36	Individual protein	Tyrosine-protein kinase SRC	Homo sapiens	IC50	=	12900.0	nM	PMID[20155932]
NPT459	Individual protein	Human immunodeficiency virus type 1 reverse transcriptase	Human immunodeficiency virus 1	Activity	=	82.2	%	PMID[12762814]
NPT728	Individual protein	Serine/threonine-protein kinase AKT	Homo sapiens	IC50	>	100000.0	nM	PMID[22418278]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1864	Cell line	L5178Y	Mus musculus	IC50	=	400.0	nM	PMID[24033101]
NPT179	Cell line	A2780	Homo sapiens	IC50	=	4340.0	nM	PMID[25563890]
NPT179	Cell line	A2780	Homo sapiens	IC50	=	26000.0	nM	PMID[25563890]
NPT737	Cell line	HUVEC	Homo sapiens	IC50	=	1800.0	nM	PMID[17368035]
NPT1231	Organism	Microbotryum violaceum	Microbotryum violaceum	IZ	=	1.0	mm	PMID[22360613]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	17.0	%	PMID[12762814]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	37.0	%	PMID[12762814]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	94.7	%	PMID[15730257]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	94.8	%	PMID[16759086]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	95.2	%	PMID[16303302]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	95.4	%	PMID[16303302]

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 NPC202157 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	32313
0.1-0.2	15356
0.2-0.3	1799
0.3-0.4	322
0.4-0.5	41
0.5-0.6	18
0.6-0.7	5
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
0.6957	Remote Similarity	NPC275734
0.6792	Remote Similarity	NPC89474
0.6545	Remote Similarity	NPC329091
0.6078	Remote Similarity	NPC151473
0.6042	Remote Similarity	NPC194856
0.5849	Remote Similarity	NPC202595
0.5625	Remote Similarity	NPC488731
0.56	Remote Similarity	NPC276930
0.5536	Remote Similarity	NPC487785
0.55	Remote Similarity	NPC241904
0.541	Remote Similarity	NPC475985
0.541	Remote Similarity	NPC139036
0.541	Remote Similarity	NPC200746
0.5294	Remote Similarity	NPC239495
0.5294	Remote Similarity	NPC169479
0.5217	Remote Similarity	NPC488730
0.5217	Remote Similarity	NPC488729
0.5185	Remote Similarity	NPC265251
0.5098	Remote Similarity	NPC61620
0.5094	Remote Similarity	NPC196277
0.5091	Remote Similarity	NPC179183
0.5091	Remote Similarity	NPC101996
0.5082	Remote Similarity	NPC474843

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC202157 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6029
0.1-0.2	3087
0.2-0.3	30
0.3-0.4	2
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