NPASS Compound

Natural Product: NPC151220

Natural Product ID	NPC151220
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MIXHWJJKSJFGCZ-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	12314461
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0001614] Neoflavonoids [CHEMONTID:0003650] Prenylated neoflavonoids

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 54 57 0 0 0 0 0 0 0 0999 V2000 5.3286 -0.1415 1.9122 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2524 -0.5344 0.9357 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3838 0.3215 -0.3182 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7469 0.0649 -0.8978 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3447 -0.0359 -1.3094 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6696 -0.4532 -2.4523 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9226 0.0781 -1.0099 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2759 1.2587 -1.2838 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0652 1.4428 -1.0286 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7034 2.7122 -1.3379 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9792 2.8466 -1.0818 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8180 1.7892 -0.4967 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4845 2.3892 0.7327 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9623 1.5654 -1.5015 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1692 0.5893 -0.2079 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8330 0.4135 -0.4704 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1773 -0.7888 -0.1927 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8818 -1.8241 0.3540 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1555 -3.0007 0.6138 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1825 -3.1085 0.3340 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8082 -4.1928 0.5836 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7849 -2.0772 -0.1892 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1903 -0.9452 -0.4626 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3021 -1.7703 0.5993 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2653 -1.7183 -0.3852 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6119 -1.6643 -0.0978 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0640 -1.6599 1.2052 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1130 -1.7116 2.2022 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7652 -1.7656 1.9177 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9832 2.3176 -1.8388 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9240 -0.2145 2.9423 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6682 0.9003 1.7007 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1982 -0.8485 1.8774 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4147 -1.5965 0.6620 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2645 -0.3672 1.4202 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3386 1.3957 -0.0312 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1098 -0.9624 -0.6930 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7253 0.1744 -1.9967 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4649 0.7849 -0.4665 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1651 3.5600 -1.7751 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4662 3.7810 -1.3054 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5357 2.0419 0.8007 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9479 2.1336 1.6671 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5102 3.4959 0.6658 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8378 1.1205 -0.9894 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6229 0.9720 -2.3571 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2754 2.5553 -1.8867 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7236 -3.8077 1.0466 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9558 -1.7227 -1.4358 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3589 -1.6238 -0.8758 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1318 -1.6170 1.4259 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4815 -1.7077 3.2387 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0430 -1.8054 2.7214 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4249 2.9610 -1.1844 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 3 5 1 0 5 6 2 0 5 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 12 14 1 0 12 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 1 0 18 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 8 30 1 0 23 7 1 0 29 24 1 0 16 9 2 0 23 17 2 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 0 2 35 1 0 3 36 1 0 4 37 1 0 4 38 1 0 4 39 1 0 10 40 1 0 11 41 1 0 13 42 1 0 13 43 1 0 13 44 1 0 14 45 1 0 14 46 1 0 14 47 1 0 19 48 1 0 25 49 1 0 26 50 1 0 27 51 1 0 28 52 1 0 29 53 1 0 30 54 1 0 M END

Standard InCHIKey	MIXHWJJKSJFGCZ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C25H24O5/c1-5-14(2)21(27)20-22(28)16-11-12-25(3,4)30-23(16)19-17(13-18(26)29-24(19)20)15-9-7-6-8-10-15/h6-14,28H,5H2,1-4H3
SMILES	CCC(C)C(=O)c1c(c2C=CC(C)(C)Oc2c2c(cc(=O)oc12)c1ccccc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	404.16	Volume:	424.317 ? Van der Waals volume.
Dense:	0.952	LogP:	5.109 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.96 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.494 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	76.74 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.454	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.384	Fsp³:	0.28
MCE-18:	79.625 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.864	Fluc inhibitor:	0.016 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.787 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.899 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.24	Promiscuous compounds:	0.062

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.867	MDCK Permeability:	-4.646
Pgp-inhibitor:	0.863	Pgp-substrate:	0.001
PAMPA:	0.238 ? 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%):	0.518	30% Bioavailability (F30%):	0.945
50% Bioavailability (F50%):	0.968

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.293	MRP1:	0.999
Plasma Protein Binding (PPB):	98.936%	Volume Distribution (VD):	-0.141
Fu:	0.602% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	0.923	BCRP inhibitor:	0.026
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.664	CYP1A2-substrate:	0.996
CYP2C19-inhibitor:	0.79	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.197	CYP2C9-substrate:	0.893
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.004
CYP3A4-inhibitor:	0.41	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.016	CYP2C8-inhibitor:	0.992
HLM stability:	0.883 ? 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):

1.706

Half-life (T1/2):

1.013

ADMET: Toxicity

hERG Blockers:	0.166	hERG Blockers (10um):	0.482
Human Hepatotoxicity (H-HT):	0.662	Drug-induced Liver Injury (DILI):	0.588
AMES Toxicity:	0.334	Rat Oral Acute Toxicity:	0.461
Maximum Recommended Daily Dose:	0.775	Skin Sensitization:	0.399
Carcinogencity:	0.651	Eye Corrosion:	0.009
Eye Irritation:	0.564	Respiratory Toxicity:	0.769
Drug-induced Neurotoxicity:	0.432	Ototoxicity:	0.31
Hematotoxicity:	0.33	Drug-induced Nephrotoxicity:	0.392
Genotoxicity:	0.704	RPMI-8226 Immunitoxicity:	0.107
A549 Cytotoxicity:	0.106	Hek293 Cytotoxicity:	0.496
BCF:	1.757 ? 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:	4.871 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.857 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.311 ? 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
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15678383]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16045947]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	stem	n.a.	PMID[20188156]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	Malaysian	n.a.	PMID[7506311]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	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 NPC151220 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	14887
0.1-0.2	32312
0.2-0.3	2345
0.3-0.4	248
0.4-0.5	32
0.5-0.6	25
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8507	High Similarity	NPC208303
0.7808	Intermediate Similarity	NPC469933
0.7083	Intermediate Similarity	NPC151973
0.6709	Remote Similarity	NPC469932
0.64	Remote Similarity	NPC475797
0.6316	Remote Similarity	NPC249942
0.6026	Remote Similarity	NPC282335
0.6026	Remote Similarity	NPC218300
0.5844	Remote Similarity	NPC321372
0.5844	Remote Similarity	NPC297886
0.5696	Remote Similarity	NPC161864
0.5658	Remote Similarity	NPC188632
0.5658	Remote Similarity	NPC112791
0.5625	Remote Similarity	NPC35501
0.5625	Remote Similarity	NPC137262
0.5625	Remote Similarity	NPC144512
0.5625	Remote Similarity	NPC278600
0.5625	Remote Similarity	NPC37428
0.5625	Remote Similarity	NPC47040
0.561	Remote Similarity	NPC469934
0.557	Remote Similarity	NPC57470
0.5432	Remote Similarity	NPC109967
0.5432	Remote Similarity	NPC469936
0.5375	Remote Similarity	NPC470322
0.5375	Remote Similarity	NPC469956
0.5366	Remote Similarity	NPC608427
0.5309	Remote Similarity	NPC279218
0.5294	Remote Similarity	NPC469955
0.5294	Remote Similarity	NPC469952
0.5119	Remote Similarity	NPC469935
0.5111	Remote Similarity	NPC472206
0.5063	Remote Similarity	NPC470296
0.5063	Remote Similarity	NPC196459

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC151220 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2104
0.1-0.2	6912
0.2-0.3	131
0.3-0.4	3
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