NPASS Compound

Natural Product: NPC473286

Natural Product ID	NPC473286
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cudratricusxanthone J
IUPAC Name	5,8,9-trihydroxy-1,1,2-trimethyl-7-(3-methylbut-2-enyl)-2H-furo[2,3-c]xanthen-6-one
Synonyms	cudratricusxanthone J
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL395246
PubChem CID	16757393
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 [CHEMONTID:0003519] 8-prenylated 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 53 56 0 0 0 0 0 0 0 0999 V2000 -5.2121 -0.4434 2.0471 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5757 -0.1444 0.6308 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6931 -0.2530 -0.3514 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2781 -0.6825 -0.0979 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3271 0.3839 -0.4372 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9592 0.0839 -0.3651 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0076 1.0301 -0.6730 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4533 2.2819 -1.0541 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7952 2.5836 -1.1265 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7653 1.6304 -0.8159 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1197 1.9600 -0.8946 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2617 3.8322 -1.5059 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2825 0.7477 -0.6046 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7488 -0.4256 -0.2467 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8638 -1.4447 0.0840 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3512 -2.6750 0.4594 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7039 -2.9208 0.5152 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5646 -1.8822 0.1787 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1126 -0.6382 -0.2014 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3086 0.1718 -0.4718 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6030 0.1654 -1.9499 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1654 1.6109 -0.0424 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3889 -0.5534 0.2664 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3972 -0.2237 1.7574 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9669 -1.9006 0.1628 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4819 -3.6976 0.7907 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4821 -1.1530 0.0133 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2635 -2.0858 0.3170 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9620 0.2833 0.3352 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8156 -1.4901 2.1474 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1038 -0.3792 2.7010 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4862 0.3032 2.4578 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0441 -0.0330 -1.3641 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2383 -1.0213 0.9437 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1179 -1.5013 -0.8430 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2827 3.0302 -1.2983 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4355 2.7092 -1.5024 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6786 4.6266 -1.6922 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1015 -3.9006 0.8137 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8273 -0.8650 -2.2724 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4106 0.8673 -2.2196 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6796 0.4634 -2.5181 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9599 1.7387 1.0259 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1068 2.1272 -0.3046 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3427 2.0465 -0.6377 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3949 -0.4095 -0.1779 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1433 0.5867 1.9670 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7455 -1.1080 2.3604 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3902 0.0211 2.1227 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7413 -4.6441 0.9323 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0369 1.3865 0.4120 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7197 -0.2389 0.9537 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2330 0.0433 -0.7265 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 9 12 1 0 7 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 20 22 1 0 20 23 1 0 23 24 1 0 23 25 1 0 16 26 1 0 15 27 1 0 27 28 2 0 2 29 1 0 10 5 1 0 19 14 1 0 27 6 1 0 25 18 1 0 1 30 1 0 1 31 1 0 1 32 1 0 3 33 1 0 4 34 1 0 4 35 1 0 8 36 1 0 11 37 1 0 12 38 1 0 17 39 1 0 21 40 1 0 21 41 1 0 21 42 1 0 22 43 1 0 22 44 1 0 22 45 1 0 23 46 1 0 24 47 1 0 24 48 1 0 24 49 1 0 26 50 1 0 29 51 1 0 29 52 1 0 29 53 1 0 M END

Standard InCHIKey	GIEMQAXHAKGAAH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C23H24O6/c1-10(2)6-7-12-17-15(9-14(25)20(12)26)29-22-18(21(17)27)13(24)8-16-19(22)23(4,5)11(3)28-16/h6,8-9,11,24-26H,7H2,1-5H3
SMILES	CC(=CCc1c2c(cc(c1O)O)oc1c(c(cc3c1C(C)(C)C(C)O3)O)c2=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	396.16	Volume:	403.788 ? Van der Waals volume.
Dense:	0.981	LogP:	4.179 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.425 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.42 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	22.0
TPSA:	100.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.332	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.834	Fsp³:	0.348
MCE-18:	87.613 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.854	Fluc inhibitor:	0.316 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.961 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.817 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.218	Promiscuous compounds:	0.18

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.957	MDCK Permeability:	-4.719
Pgp-inhibitor:	0.683	Pgp-substrate:	0.657
PAMPA:	0.147 ? 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):	0.084
20% Bioavailability (F20%):	0.964	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.987
Plasma Protein Binding (PPB):	95.496%	Volume Distribution (VD):	0.124
Fu:	4.948% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.72	BCRP inhibitor:	0.987
BSEP inhibitor:	0.986

ADMET: Metabolism

CYP1A2-inhibitor:	0.004	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.023	CYP2C9-substrate:	0.105
CYP2D6-inhibitor:	0.022	CYP2D6-substrate:	0.186
CYP3A4-inhibitor:	0.877	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

6.442

Half-life (T1/2):

1.602

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.493
Human Hepatotoxicity (H-HT):	0.484	Drug-induced Liver Injury (DILI):	0.907
AMES Toxicity:	0.653	Rat Oral Acute Toxicity:	0.821
Maximum Recommended Daily Dose:	0.658	Skin Sensitization:	0.931
Carcinogencity:	0.69	Eye Corrosion:	0.004
Eye Irritation:	0.903	Respiratory Toxicity:	0.942
Drug-induced Neurotoxicity:	0.05	Ototoxicity:	0.308
Hematotoxicity:	0.133	Drug-induced Nephrotoxicity:	0.284
Genotoxicity:	0.943	RPMI-8226 Immunitoxicity:	0.037
A549 Cytotoxicity:	0.372	Hek293 Cytotoxicity:	0.535
BCF:	2.065 ? 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:	4.776 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.726 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.049 ? 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
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15787460]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[15787460]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16203143]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16919944]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	root bark	n.a.	n.a.	PMID[17608532]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17950599]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	fruits	n.a.	n.a.	PMID[19113968]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	Roots	n.a.	n.a.	PMID[19191562]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[19280148]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19285413]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19660948]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[21319773]
NPO8797	Cudrania tricuspidata	Species	Moraceae	Eukaryota	Root barks	n.a.	n.a.	PMID[25051453]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	Roots	n.a.	n.a.	PMID[25322455]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	root barks	purchased from the local herbal market, Chungbuk, Korea	2012-JUL	PMID[26227773]
NPO8797	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27420919]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8797	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO30804	Cudrania tricuspidata	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8797	Cudrania tricuspidata	Species	Moraceae	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	1
EC50	2

Activity Type	# Activity
Individual protein	1
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT892	Individual protein	Monoamine oxidase A	Mus musculus	IC50	>	150000.0	nM	PMID[26216016]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	EC50	=	8100.0	nM	PMID[27420919]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	EC50	>	50000.0	nM	PMID[27420919]

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 NPC473286 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	22137
0.1-0.2	24659
0.2-0.3	2766
0.3-0.4	241
0.4-0.5	39
0.5-0.6	13
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
0.7536	Intermediate Similarity	NPC32694
0.6197	Remote Similarity	NPC235018
0.6026	Remote Similarity	NPC481615
0.5974	Remote Similarity	NPC478522
0.575	Remote Similarity	NPC187354
0.5714	Remote Similarity	NPC89474
0.5676	Remote Similarity	NPC604618
0.5488	Remote Similarity	NPC481610
0.5417	Remote Similarity	NPC142339
0.5405	Remote Similarity	NPC472281
0.5333	Remote Similarity	NPC45146
0.5238	Remote Similarity	NPC481611
0.5185	Remote Similarity	NPC329760
0.5181	Remote Similarity	NPC321896
0.5065	Remote Similarity	NPC478719
0.5059	Remote Similarity	NPC481613

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473286 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4013
0.1-0.2	5109
0.2-0.3	26
0.3-0.4	2
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