NPASS Compound

Natural Product: NPC472052

Natural Product ID	NPC472052
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	YMUYQXVUCQBXAD-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3335040
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000018] Anthracenes [CHEMONTID:0000151] Anthraquinones [CHEMONTID:0001598] Hydroxyanthraquinones

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 64 69 0 0 0 0 0 0 0 0999 V2000 1.7244 4.8430 -1.6617 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6893 3.5246 -0.9579 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7808 2.6822 -0.9994 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7463 1.4619 -0.3471 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5974 1.1162 0.3401 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4930 1.9362 0.3990 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5453 3.1464 -0.2559 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5690 3.9699 -0.1945 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6626 1.4687 1.1527 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7872 1.7539 2.4910 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8520 1.3443 3.2647 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8359 0.6107 2.6492 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7197 0.3162 1.2942 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6498 0.7326 0.5353 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5506 0.4057 -0.9042 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5532 0.8181 -1.5212 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6171 -0.3748 -1.5158 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7022 -0.8076 -0.7852 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7802 -0.4750 0.6293 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7566 -0.8535 1.3281 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6873 -1.5473 -1.4209 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6322 -1.8732 -2.7606 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5402 -1.4324 -3.4764 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5446 -0.6906 -2.8559 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4379 -0.2458 -3.5886 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6427 -2.6247 -3.3852 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7509 -3.0561 -2.6000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9272 1.6915 4.7281 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1924 2.4974 3.1524 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5764 -0.1710 1.0214 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5465 -0.5462 1.6715 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7067 -1.0936 1.0046 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8457 -0.7294 0.3121 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8916 0.5587 -0.3807 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9478 0.8726 -1.0103 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9055 -1.6086 0.3038 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8703 -2.8267 0.9553 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7198 -3.1755 1.6448 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6422 -2.3129 1.6696 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4722 -2.6320 2.3522 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9766 -3.6836 0.9147 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1252 -3.2807 0.1978 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8357 5.4338 -1.3491 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7473 4.6464 -2.7410 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6335 5.3935 -1.3442 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6690 2.9973 -1.5556 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1654 4.1727 -0.9889 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6975 0.2589 3.1991 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5167 -1.8674 -0.8215 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4911 -1.6881 -4.5405 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3172 -0.4991 -4.5517 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4582 -3.8668 -1.8956 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5838 -3.4080 -3.2306 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1415 -2.1739 -2.0143 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1474 0.8183 5.3412 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9516 2.1242 5.0125 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7348 2.4708 4.7952 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1024 3.4993 3.0860 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7870 -1.2974 -0.2475 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6680 -4.1390 2.1706 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7345 -3.0743 1.8099 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7988 -2.9721 -0.8349 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8136 -4.1351 0.0453 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6191 -2.4036 0.6498 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 2 0 5 6 1 0 6 7 2 0 7 8 1 0 6 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 18 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 22 26 1 0 26 27 1 0 11 28 1 0 10 29 1 0 5 30 1 0 30 31 2 0 30 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 33 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 39 40 1 0 37 41 1 0 41 42 1 0 7 2 1 0 34 4 1 0 14 9 1 0 19 13 1 0 24 17 1 0 39 32 1 0 1 43 1 0 1 44 1 0 1 45 1 0 3 46 1 0 8 47 1 0 12 48 1 0 21 49 1 0 23 50 1 0 25 51 1 0 27 52 1 0 27 53 1 0 27 54 1 0 28 55 1 0 28 56 1 0 28 57 1 0 29 58 1 0 36 59 1 0 38 60 1 0 40 61 1 0 42 62 1 0 42 63 1 0 42 64 1 0 M END

Standard InCHIKey	YMUYQXVUCQBXAD-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C32H22O10/c1-11-5-15-23(31(39)21-17(29(15)37)7-13(41-3)9-19(21)33)25(27(11)35)26-24-16(6-12(2)28(26)36)30(38)18-8-14(42-4)10-20(34)22(18)32(24)40/h5-10,33-36H,1-4H3
SMILES	CC1=CC2=C(C(=C1O)C3=C(C(=CC4=C3C(=O)C5=C(C4=O)C=C(C=C5O)OC)C)O)C(=O)C6=C(C2=O)C=C(C=C6O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	566.12	Volume:	556.408 ? Van der Waals volume.
Dense:	1.017	LogP:	5.868 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.377 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-10.501 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	167.66 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.242	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.98	Fsp³:	0.125
MCE-18:	80.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	1
Colloidal aggregators:	0.958	Fluc inhibitor:	0.253 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.02 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.971 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.368	Promiscuous compounds:	0.198

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.308	MDCK Permeability:	-4.876
Pgp-inhibitor:	0.999	Pgp-substrate:	0.017
PAMPA:	0.556 ? 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):	0.769
20% Bioavailability (F20%):	0.084	30% Bioavailability (F30%):	0.971
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.857
Plasma Protein Binding (PPB):	97.315%	Volume Distribution (VD):	0.669
Fu:	1.838% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.967
BSEP inhibitor:	0.965

ADMET: Metabolism

CYP1A2-inhibitor:	0.998	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.108	CYP2C19-substrate:	0.988
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.986
CYP2D6-inhibitor:	0.019	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.842 ? 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):

2.239

Half-life (T1/2):

1.551

ADMET: Toxicity

hERG Blockers:	0.196	hERG Blockers (10um):	0.656
Human Hepatotoxicity (H-HT):	0.911	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.994	Rat Oral Acute Toxicity:	0.611
Maximum Recommended Daily Dose:	0.873	Skin Sensitization:	0.893
Carcinogencity:	0.965	Eye Corrosion:	0.0
Eye Irritation:	0.877	Respiratory Toxicity:	0.963
Drug-induced Neurotoxicity:	0.676	Ototoxicity:	0.837
Hematotoxicity:	0.987	Drug-induced Nephrotoxicity:	0.968
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.814
A549 Cytotoxicity:	0.999	Hek293 Cytotoxicity:	0.933
BCF:	1.399 ? 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:	4.799 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.007 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.706 ? 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
NPO33215	Stemphylium sp. 33231	Species	Pleosporaceae	Eukaryota	n.a.	South China Sea	n.a.	PMID[25136754]
NPO33215	Stemphylium sp. 33231	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	7
IC50	2

Activity Type	# Activity
Cell line	1
Organism	7
Non-molecular	1

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
NPT81	Cell line	A549	Homo sapiens	IC50	>	10000.0	nM	DrugMatrix in vivo data: Pathology
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[25136754]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	>	10000.0	nM	PMID[12027740]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	10000.0	nM	PMID[18183025]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	10000.0	nM	PMID[19053514]
NPT314	Organism	Bacillus cereus	Bacillus cereus	MIC	=	8100.0	nM	PMID[14738378]
NPT3146	Organism	Micrococcus	Micrococcus	MIC	>	10000.0	nM	Open TG-GATES in vivo data: Organ Weight
NPT1238	Organism	Staphylococcus	Staphylococcus	MIC	>	10000.0	nM	PMID[21534539]
NPT3147	Organism	Kocuria rhizophila	Kocuria rhizophila	MIC	>	10000.0	nM	PubChem BioAssay data set

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 NPC472052 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	22896
0.1-0.2	21553
0.2-0.3	5141
0.3-0.4	237
0.4-0.5	17
0.5-0.6	9
0.6-0.7	3
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
0.7091	Intermediate Similarity	NPC470342
0.6964	Remote Similarity	NPC472060
0.6383	Remote Similarity	NPC126767
0.6383	Remote Similarity	NPC107109
0.5833	Remote Similarity	NPC312929
0.5735	Remote Similarity	NPC105414
0.5714	Remote Similarity	NPC294646
0.5625	Remote Similarity	NPC56433
0.56	Remote Similarity	NPC118027
0.5493	Remote Similarity	NPC470341
0.5493	Remote Similarity	NPC472058
0.5306	Remote Similarity	NPC134191
0.5306	Remote Similarity	NPC19896

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC472052 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4270
0.1-0.2	4732
0.2-0.3	144
0.3-0.4	4
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