NPASS Compound

Natural Product: NPC511205

Natural Product ID	NPC511205
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Philonotisflavone
IUPAC Name	8-[6-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2,3-dihydroxy-phenyl]-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-chromen-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 60 65 0 0 0 0 0 0 0 0999 V2000 1.2229 2.4308 -1.9174 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8876 1.5975 -1.2495 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3578 0.3669 -1.0064 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0160 -0.6206 -0.2786 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4101 -1.9379 -0.0382 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8355 -2.9901 -0.8298 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2746 -4.2327 -0.6517 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2844 -4.4233 0.3217 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2888 -5.6753 0.5090 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1568 -3.3930 1.1230 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1361 -3.5601 2.0907 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4362 -2.1518 0.9121 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0342 -1.0673 1.7427 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7026 -0.8525 2.9243 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7735 -1.6718 3.3486 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3744 0.1783 3.7794 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6682 1.0339 3.4398 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0143 2.0730 4.2811 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3526 0.8381 2.2599 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0049 -0.1988 1.4235 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6921 -0.3328 0.3160 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6826 0.4342 -0.0673 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3834 0.1815 -1.3465 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0298 -0.8719 -2.1590 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6411 -1.1422 -3.3560 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6659 -0.3322 -3.7917 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2875 -0.6057 -5.0075 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0420 0.7261 -3.0047 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0737 1.5376 -3.4493 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4040 0.9902 -1.7773 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0454 1.4765 0.7554 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3852 1.7101 1.9524 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7033 2.6593 2.7196 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1872 -0.3166 0.1734 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7569 0.8563 -0.0267 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0182 1.1555 0.4711 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5849 2.3888 0.2449 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8517 2.7450 0.7217 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9255 3.3752 -0.4831 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6873 3.0959 -0.9776 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9774 4.0401 -1.7124 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1389 1.8745 -0.7475 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3844 0.1262 -1.3923 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6125 -2.8050 -1.5825 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5906 -5.0864 -1.2625 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2986 -6.5006 0.4430 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1009 -3.4737 1.7320 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6806 -1.2725 3.4317 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9177 0.3213 4.6996 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6645 3.0052 4.0209 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2178 -1.4983 -1.7970 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3463 -1.9845 -3.9890 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1048 -0.0671 -5.3012 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3914 2.3037 -2.8695 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7455 1.8268 -1.2201 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8570 2.1535 0.5050 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5458 0.4151 1.0340 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5748 2.0622 0.8571 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3431 4.3412 -0.6736 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3999 4.7441 -1.2276 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 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 10 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 14 16 1 0 16 17 2 0 17 18 1 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 26 28 1 0 28 29 1 0 28 30 2 0 22 31 2 0 31 32 1 0 32 33 2 0 4 34 1 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 1 0 37 39 2 0 39 40 1 0 40 41 1 0 40 42 2 0 42 2 1 0 12 5 1 0 20 13 1 0 30 23 1 0 42 35 1 0 32 19 1 0 3 43 1 0 6 44 1 0 7 45 1 0 9 46 1 0 11 47 1 0 15 48 1 0 16 49 1 0 18 50 1 0 24 51 1 0 25 52 1 0 27 53 1 0 29 54 1 0 30 55 1 0 31 56 1 0 36 57 1 0 38 58 1 0 39 59 1 0 41 60 1 0 M END

Standard InCHIKey	MJRDPDQSEGRCID-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C30H18O12/c31-12-6-17(35)26-20(38)10-23(41-24(26)7-12)13-2-4-15(33)29(40)25(13)28-19(37)8-18(36)27-21(39)9-22(42-30(27)28)11-1-3-14(32)16(34)5-11/h1-10,31-37,40H
SMILES	O=C1C=C(C2=CC=C(O)C(O)=C2C2=C(O)C=C(O)C3=C2OC(C2=CC=C(O)C(O)=C2)=CC3=O)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	570.08	Volume:	539.397 ? Van der Waals volume.
Dense:	1.057	LogP:	3.128 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.019 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.017 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	222.26 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	8.0	Rings:	6.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.137	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.251	Fsp³:	0.0
MCE-18:	38.0 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.989	Fluc inhibitor:	0.631 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.754 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.922 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.682	Promiscuous compounds:	0.951

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.984	MDCK Permeability:	-4.879
Pgp-inhibitor:	0.0	Pgp-substrate:	0.269
PAMPA:	0.409 ? 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):	0.001
20% Bioavailability (F20%):	0.939	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.931
Plasma Protein Binding (PPB):	96.627%	Volume Distribution (VD):	-0.541
Fu:	3.315% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.928
OATP1B3 inhibitor:	0.987	BCRP inhibitor:	0.983
BSEP inhibitor:	0.141

ADMET: Metabolism

CYP1A2-inhibitor:	0.235	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.277	CYP2C9-substrate:	0.271
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.091
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.82 ? 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):

3.515

Half-life (T1/2):

2.479

ADMET: Toxicity

hERG Blockers:	0.026	hERG Blockers (10um):	0.581
Human Hepatotoxicity (H-HT):	0.345	Drug-induced Liver Injury (DILI):	0.977
AMES Toxicity:	0.795	Rat Oral Acute Toxicity:	0.624
Maximum Recommended Daily Dose:	0.985	Skin Sensitization:	0.965
Carcinogencity:	0.672	Eye Corrosion:	0.002
Eye Irritation:	0.998	Respiratory Toxicity:	0.882
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.102
Hematotoxicity:	0.007	Drug-induced Nephrotoxicity:	0.003
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.059
A549 Cytotoxicity:	0.957	Hek293 Cytotoxicity:	0.96
BCF:	1.078 ? 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:	4.254 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.752 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.494 ? 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
NPO8970	Citrullus lanatus	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14435	Mnium hornum	Species	Mniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25263	Aulacomnium androgynum	Species	Aulacomniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO51807	Bartramia stricta	Species	Bartramiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO51079	Philonotis fontana	Species	Bartramiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8970	Citrullus lanatus	Species	Cucurbitaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO8970	Citrullus lanatus	Species	Cucurbitaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO8970	Citrullus lanatus	Species	Cucurbitaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO8970	Citrullus lanatus	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14435	Mnium hornum	Species	Mniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25263	Aulacomnium androgynum	Species	Aulacomniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8970	Citrullus lanatus	Species	Cucurbitaceae	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 NPC511205 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	39470
0.1-0.2	8613
0.2-0.3	1130
0.3-0.4	529
0.4-0.5	88
0.5-0.6	20
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	Natural Product ID
0.7463	Intermediate Similarity	NPC610480
0.7119	Intermediate Similarity	NPC279121
0.7059	Intermediate Similarity	NPC254351
0.6377	Remote Similarity	NPC138299
0.6027	Remote Similarity	NPC603692
0.5968	Remote Similarity	NPC50898
0.5873	Remote Similarity	NPC222713
0.5873	Remote Similarity	NPC175013
0.5833	Remote Similarity	NPC288840
0.5733	Remote Similarity	NPC259757
0.5714	Remote Similarity	NPC71061
0.5714	Remote Similarity	NPC67322
0.5714	Remote Similarity	NPC303485
0.5606	Remote Similarity	NPC610974
0.5469	Remote Similarity	NPC78540
0.5385	Remote Similarity	NPC150908
0.5303	Remote Similarity	NPC274121
0.5224	Remote Similarity	NPC213216
0.5211	Remote Similarity	NPC52005
0.5152	Remote Similarity	NPC275772
0.5152	Remote Similarity	NPC20791
0.5139	Remote Similarity	NPC183950
0.5125	Remote Similarity	NPC290830
0.5075	Remote Similarity	NPC179271
0.5067	Remote Similarity	NPC111112

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC511205 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7924
0.1-0.2	1195
0.2-0.3	26
0.3-0.4	3
0.4-0.5	0
0.5-0.6	1
0.6-0.7	0
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
0.7119	Intermediate Similarity	NPD1511	Phase 2
0.5152	Remote Similarity	NPD1512	Phase 3

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