NPASS Compound

Natural Product: NPC572221

Natural Product ID	NPC572221
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-6-[4-[(2~{S})-5,7-dihydroxy-4-oxo-chroman-2-yl]phenoxy]-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one
IUPAC Name	(2~{S})-6-[4-[(2~{S})-5,7-dihydroxy-4-oxo-chroman-2-yl]phenoxy]-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 6.4698 -0.0796 2.7036 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3812 -0.7238 1.6349 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7586 -2.0677 1.5214 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8842 -2.1281 0.3090 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5108 -1.6417 0.6635 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4908 -2.5151 0.9895 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2114 -2.0611 1.3196 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9902 -0.6773 1.3101 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2361 -0.1675 1.6225 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3029 0.0882 0.8107 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4530 1.3194 0.2061 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5321 2.3666 0.3890 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5601 1.4939 -0.6001 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5100 0.5213 -0.8310 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6155 0.7128 -1.6433 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8211 0.0156 -1.5110 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.7626 0.7465 -0.6087 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3466 1.2925 0.5957 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1964 1.9645 1.4328 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5235 2.1283 1.1059 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3853 2.8160 1.9661 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.9594 1.5935 -0.0875 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0950 0.9161 -0.9273 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6699 -1.4202 -1.1267 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3718 -1.7277 -0.4791 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1392 -2.8991 -0.1393 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3608 -0.7090 -0.2267 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2626 -0.9082 0.5837 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1662 -2.1604 1.1639 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0186 0.1804 0.9829 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2906 -0.2740 0.6548 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4086 -1.4865 -0.8150 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4085 -0.5360 -0.8022 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9058 0.0149 -1.9729 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9088 0.9684 -1.9608 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4060 1.5197 -3.1403 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4018 1.3552 -0.7235 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9185 0.8178 0.4461 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4102 1.2034 1.6846 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9197 -0.1302 0.4119 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1266 -2.2070 2.4202 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5284 -2.8699 1.4245 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7534 -3.2152 0.0401 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6571 -3.5686 0.9971 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4261 -2.7550 1.5763 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3727 2.7122 1.3473 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6727 2.4557 -1.0697 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3110 0.0300 -2.5252 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3164 1.1890 0.8932 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8626 2.3956 2.3864 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2958 3.8422 2.0066 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9939 1.7195 -0.3454 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4376 0.4896 -1.8767 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4597 -1.7177 -0.3759 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7911 -2.1286 -1.9720 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5518 -2.4209 2.0424 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8230 1.2398 0.9898 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0616 0.4381 0.4058 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5238 -0.2840 -2.9430 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6030 0.9313 -3.9611 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1930 2.1068 -0.7068 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9453 1.8952 2.2687 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 9 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 20 22 1 0 22 23 2 0 16 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 2 0 28 29 1 0 8 30 1 0 30 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 28 10 1 0 27 14 1 0 23 17 1 0 3 41 1 0 3 42 1 0 4 43 1 6 6 44 1 0 7 45 1 0 12 46 1 0 13 47 1 0 16 48 1 6 18 49 1 0 19 50 1 0 21 51 1 0 22 52 1 0 23 53 1 0 24 54 1 0 24 55 1 0 29 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	HTBWACDSWNWBGQ-ZEQRLZLVSA-N
Standard InCHI	InChI=1S/C30H22O10/c31-16-5-1-14(2-6-16)24-12-21(35)28-26(40-24)13-22(36)30(29(28)37)38-18-7-3-15(4-8-18)23-11-20(34)27-19(33)9-17(32)10-25(27)39-23/h1-10,13,23-24,31-33,36-37H,11-12H2/t23-,24-/m0/s1
SMILES	O=C1C[C@@H](C2=CC=C(OC3=C(O)C=C4O[C@H](C5=CC=C(O)C=C5)CC(=O)C4=C3O)C=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:	3.914 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.247 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.68 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	36.0
TPSA:	162.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.225	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.772	Fsp³:	0.133
MCE-18:	113.235 ? 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:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.996	Fluc inhibitor:	0.666 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.483 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.87 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.419	Promiscuous compounds:	0.042

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.596	MDCK Permeability:	-4.853
Pgp-inhibitor:	1.0	Pgp-substrate:	0.02
PAMPA:	0.335 ? 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%):	0.989
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.9
Plasma Protein Binding (PPB):	96.835%	Volume Distribution (VD):	-0.128
Fu:	3.626% ? 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:	0.152	CYP1A2-substrate:	0.381
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.135	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.179	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.018
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.834
HLM stability:	0.985 ? 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):

3.262

Half-life (T1/2):

1.721

ADMET: Toxicity

hERG Blockers:	0.156	hERG Blockers (10um):	0.597
Human Hepatotoxicity (H-HT):	0.834	Drug-induced Liver Injury (DILI):	0.791
AMES Toxicity:	0.885	Rat Oral Acute Toxicity:	0.576
Maximum Recommended Daily Dose:	0.921	Skin Sensitization:	0.638
Carcinogencity:	0.813	Eye Corrosion:	0.0
Eye Irritation:	0.987	Respiratory Toxicity:	0.13
Drug-induced Neurotoxicity:	0.529	Ototoxicity:	0.51
Hematotoxicity:	0.087	Drug-induced Nephrotoxicity:	0.518
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.181
A549 Cytotoxicity:	0.884	Hek293 Cytotoxicity:	0.973
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:	4.625 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.66 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.187 ? 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
NPO18228	Cycas beddomei	Species	Cycadaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18228	Cycas beddomei	Species	Cycadaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18228	Cycas beddomei	Species	Cycadaceae	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

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 NPC572221 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	28368
0.1-0.2	18728
0.2-0.3	2083
0.3-0.4	487
0.4-0.5	142
0.5-0.6	31
0.6-0.7	13
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
0.7455	Intermediate Similarity	NPC32441
0.7455	Intermediate Similarity	NPC79943
0.7377	Intermediate Similarity	NPC477841
0.65	Remote Similarity	NPC321011
0.65	Remote Similarity	NPC294852
0.65	Remote Similarity	NPC188679
0.6333	Remote Similarity	NPC274784
0.6333	Remote Similarity	NPC20709
0.629	Remote Similarity	NPC302950
0.6271	Remote Similarity	NPC243083
0.6271	Remote Similarity	NPC13768
0.6271	Remote Similarity	NPC287246
0.623	Remote Similarity	NPC606248
0.6094	Remote Similarity	NPC236637
0.6	Remote Similarity	NPC295261
0.6	Remote Similarity	NPC296490
0.5833	Remote Similarity	NPC182421
0.5775	Remote Similarity	NPC69531
0.5775	Remote Similarity	NPC611447
0.5556	Remote Similarity	NPC338131
0.5556	Remote Similarity	NPC107586
0.5556	Remote Similarity	NPC329203
0.5556	Remote Similarity	NPC324386
0.5556	Remote Similarity	NPC222342
0.5513	Remote Similarity	NPC479054
0.5507	Remote Similarity	NPC109223
0.5507	Remote Similarity	NPC10937
0.5507	Remote Similarity	NPC477840
0.5484	Remote Similarity	NPC12296
0.5467	Remote Similarity	NPC224851
0.5312	Remote Similarity	NPC300668
0.5246	Remote Similarity	NPC329225
0.5246	Remote Similarity	NPC147686
0.5238	Remote Similarity	NPC603284
0.5231	Remote Similarity	NPC469764
0.5231	Remote Similarity	NPC475267
0.5211	Remote Similarity	NPC134171
0.5205	Remote Similarity	NPC312973
0.5139	Remote Similarity	NPC108456
0.5114	Remote Similarity	NPC219927
0.5114	Remote Similarity	NPC611172
0.5079	Remote Similarity	NPC225153
0.5079	Remote Similarity	NPC479876
0.5077	Remote Similarity	NPC255106
0.5077	Remote Similarity	NPC235165
0.5072	Remote Similarity	NPC258630
0.507	Remote Similarity	NPC470135

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC572221 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5501
0.1-0.2	3591
0.2-0.3	45
0.3-0.4	9
0.4-0.5	0
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
0.7455	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.629	Remote Similarity	NPD1934	Phase 0
0.6271	Remote Similarity	NPD1550	Phase 2
0.5246	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