NPASS Compound

Natural Product: NPC571007

Natural Product ID	NPC571007
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-2-[3-[5-[(2~{R})-5,7-dihydroxy-4-oxo-chroman-2-yl]-2-hydroxy-phenyl]-4-hydroxy-phenyl]-5,7-dihydroxy-chroman-4-one
IUPAC Name	(2~{S})-2-[3-[5-[(2~{R})-5,7-dihydroxy-4-oxo-chroman-2-yl]-2-hydroxy-phenyl]-4-hydroxy-phenyl]-5,7-dihydroxy-chroman-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0001632] Flavanones

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 62 67 0 0 0 0 0 0 0 0999 V2000 6.5952 -1.6097 2.1305 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0408 -0.9580 1.2097 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7810 -0.1907 1.4216 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9638 -0.1695 0.1572 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9471 0.9132 0.1690 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3113 2.2251 -0.1032 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3110 3.1720 -0.0724 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9876 2.8601 0.2149 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0199 3.8375 0.2350 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6310 1.5550 0.4847 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7469 1.1678 0.7935 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6008 0.8027 -0.2280 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9089 0.4275 -0.0080 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8421 0.0312 -1.0972 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8966 -1.4540 -1.1876 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2106 -2.0390 -0.8927 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3557 -3.2719 -1.0099 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3646 -1.2611 -0.4681 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5380 -1.8688 -0.0736 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5612 -3.2592 -0.1024 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6149 -1.1074 0.3236 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5109 0.2703 0.3238 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6083 1.0281 0.7281 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3257 0.8557 -0.0754 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2383 0.1091 -0.4758 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0575 0.6656 -0.8743 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3512 0.4276 1.2976 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5332 0.7855 2.3552 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2371 1.1512 2.0780 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4193 1.5090 3.1349 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6328 0.6075 0.4537 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7554 0.0233 -0.9949 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0128 -0.4823 -1.1771 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6229 -0.5001 -2.4369 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8934 -1.0098 -2.6274 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4229 -0.9887 -3.9087 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5622 -1.5102 -1.5324 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9727 -1.4988 -0.2855 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6089 -1.9922 0.8458 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6924 -0.9853 -0.0929 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2122 -0.6749 2.2364 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0687 0.8205 1.7727 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4335 -1.1337 0.0743 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3401 2.4670 -0.3265 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5626 4.2040 -0.2803 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7961 3.7238 0.8080 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2147 0.8147 -1.2512 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4073 0.4068 -2.0598 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5912 -1.8384 -2.2001 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1591 -1.9225 -0.4809 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1908 -3.7433 0.4985 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5220 -1.6054 0.6278 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6097 2.0059 0.4627 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2873 1.9563 -0.0595 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3649 0.1418 1.5163 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9153 0.7751 3.3815 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0719 0.8655 3.8115 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3197 -0.4257 0.6729 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0748 -0.1010 -3.2775 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3289 -0.1883 -4.5360 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5368 -1.9054 -1.6566 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4098 -2.9112 1.2064 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 8 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 19 20 1 0 19 21 1 0 21 22 2 0 22 23 1 0 22 24 1 0 24 25 2 0 25 26 1 0 13 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 10 31 2 0 4 32 1 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 1 0 35 37 2 0 37 38 1 0 38 39 1 0 38 40 2 0 40 2 1 0 31 5 1 0 40 33 1 0 29 11 1 0 26 14 1 0 25 18 1 0 3 41 1 0 3 42 1 0 4 43 1 6 6 44 1 0 7 45 1 0 9 46 1 0 12 47 1 0 14 48 1 6 15 49 1 0 15 50 1 0 20 51 1 0 21 52 1 0 23 53 1 0 24 54 1 0 27 55 1 0 28 56 1 0 30 57 1 0 31 58 1 0 34 59 1 0 36 60 1 0 37 61 1 0 39 62 1 0 M END

Standard InCHIKey	DAYMIXJCSHDNJF-WMPKNSHKSA-N
Standard InCHI	InChI=1S/C30H22O10/c31-15-7-21(35)29-23(37)11-25(39-27(29)9-15)13-1-3-19(33)17(5-13)18-6-14(2-4-20(18)34)26-12-24(38)30-22(36)8-16(32)10-28(30)40-26/h1-10,25-26,31-36H,11-12H2/t25-,26+
SMILES	O=C1C[C@@H](C2=CC=C(O)C(C3=CC([C@H]4CC(=O)C5=C(O)C=C(O)C=C5O4)=CC=C3O)=C2)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	542.12	Volume:	527.089 ? Van der Waals volume.
Dense:	1.029	LogP:	4.026 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.22 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.532 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	173.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.207	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.824	Fsp³:	0.133
MCE-18:	116.471 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.989	Fluc inhibitor:	0.443 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.58 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.713 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.522	Promiscuous compounds:	0.09

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.657	MDCK Permeability:	-4.877
Pgp-inhibitor:	0.998	Pgp-substrate:	0.016
PAMPA:	0.489 ? 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):	0.0
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.953
Plasma Protein Binding (PPB):	96.287%	Volume Distribution (VD):	0.138
Fu:	5.445% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	1.0
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.878
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.981
CYP2C9-inhibitor:	0.997	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.774	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.06
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.997 ? 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):

4.31

Half-life (T1/2):

1.904

ADMET: Toxicity

hERG Blockers:	0.126	hERG Blockers (10um):	0.544
Human Hepatotoxicity (H-HT):	0.783	Drug-induced Liver Injury (DILI):	0.86
AMES Toxicity:	0.931	Rat Oral Acute Toxicity:	0.818
Maximum Recommended Daily Dose:	0.988	Skin Sensitization:	0.414
Carcinogencity:	0.811	Eye Corrosion:	0.0
Eye Irritation:	0.971	Respiratory Toxicity:	0.685
Drug-induced Neurotoxicity:	0.192	Ototoxicity:	0.45
Hematotoxicity:	0.051	Drug-induced Nephrotoxicity:	0.591
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.388
A549 Cytotoxicity:	0.975	Hek293 Cytotoxicity:	0.991
BCF:	1.49 ? 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:	4.436 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.232 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.623 ? 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
NPO55330	Homalothecium lutescens	Species	Brachytheciaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO61630	Pilotrichella cuspidata	Genus	Lembophyllaceae	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

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

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 NPC571007 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	25911
0.1-0.2	20411
0.2-0.3	2716
0.3-0.4	595
0.4-0.5	154
0.5-0.6	43
0.6-0.7	17
0.7-0.8	1
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
0.7931	Intermediate Similarity	NPC611447
0.76	Intermediate Similarity	NPC32441
0.76	Intermediate Similarity	NPC79943
0.75	Intermediate Similarity	NPC321011
0.75	Intermediate Similarity	NPC294852
0.75	Intermediate Similarity	NPC188679
0.6923	Remote Similarity	NPC243083
0.6923	Remote Similarity	NPC13768
0.6923	Remote Similarity	NPC287246
0.6731	Remote Similarity	NPC182421
0.6667	Remote Similarity	NPC274784
0.6667	Remote Similarity	NPC20709
0.6667	Remote Similarity	NPC236637
0.6604	Remote Similarity	NPC295261
0.6604	Remote Similarity	NPC296490
0.65	Remote Similarity	NPC109223
0.65	Remote Similarity	NPC10937
0.6364	Remote Similarity	NPC338131
0.6364	Remote Similarity	NPC107586
0.6333	Remote Similarity	NPC477841
0.6316	Remote Similarity	NPC302950
0.6296	Remote Similarity	NPC12296
0.6	Remote Similarity	NPC258630
0.5974	Remote Similarity	NPC66441
0.5846	Remote Similarity	NPC312973
0.5823	Remote Similarity	NPC182555
0.5789	Remote Similarity	NPC300668
0.5758	Remote Similarity	NPC88964
0.5714	Remote Similarity	NPC17170
0.5625	Remote Similarity	NPC134171
0.5625	Remote Similarity	NPC106976
0.5538	Remote Similarity	NPC108456
0.5517	Remote Similarity	NPC329203
0.5517	Remote Similarity	NPC324386
0.5517	Remote Similarity	NPC222342
0.5441	Remote Similarity	NPC118256
0.5424	Remote Similarity	NPC469764
0.5373	Remote Similarity	NPC470890
0.5373	Remote Similarity	NPC200761
0.5373	Remote Similarity	NPC475790
0.5362	Remote Similarity	NPC473272
0.5303	Remote Similarity	NPC174953
0.5303	Remote Similarity	NPC85121
0.5294	Remote Similarity	NPC69531
0.5224	Remote Similarity	NPC134783
0.5217	Remote Similarity	NPC272502
0.5217	Remote Similarity	NPC51760
0.5211	Remote Similarity	NPC224851
0.5211	Remote Similarity	NPC474038
0.5179	Remote Similarity	NPC329225
0.5179	Remote Similarity	NPC147686
0.5172	Remote Similarity	NPC201227
0.5172	Remote Similarity	NPC258474
0.5172	Remote Similarity	NPC603284
0.5167	Remote Similarity	NPC606248
0.5143	Remote Similarity	NPC474021
0.5139	Remote Similarity	NPC227579
0.5139	Remote Similarity	NPC214166
0.5139	Remote Similarity	NPC475784
0.5085	Remote Similarity	NPC1612
0.5085	Remote Similarity	NPC183959
0.5082	Remote Similarity	NPC310135
0.5072	Remote Similarity	NPC473990
0.5068	Remote Similarity	NPC111786
0.5068	Remote Similarity	NPC67396
0.5067	Remote Similarity	NPC602605

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC571007 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4754
0.1-0.2	4330
0.2-0.3	51
0.3-0.4	10
0.4-0.5	1
0.5-0.6	1
0.6-0.7	2
0.7-0.8	1
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
0.76	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD1550	Phase 2
0.6316	Remote Similarity	NPD1934	Phase 0
0.5179	Remote Similarity	NPD1549	Phase 2

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