NPASS Compound

Natural Product: NPC599909

Natural Product ID	NPC599909
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UJIJNWKXNAZKOA-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL5272077
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 56 60 0 0 0 0 0 0 0 0999 V2000 -0.4418 2.0249 2.6691 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0961 2.3568 1.3486 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1934 2.7394 1.0615 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5076 3.0588 -0.2347 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5643 3.0045 -1.2478 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7093 2.6211 -0.9333 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0662 2.2940 0.3458 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3365 1.9116 0.6605 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1056 0.9488 0.0659 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8382 1.2567 -1.0538 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6126 0.3123 -1.6633 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6876 -0.9594 -1.1884 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9458 -1.2773 -0.0513 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1669 -0.3311 0.5628 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0210 -2.6523 0.4792 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9135 -2.9808 1.4191 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5653 -2.7737 0.8620 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4938 -2.6927 1.6884 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7562 -2.5058 1.1773 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9523 -2.3953 -0.1972 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1526 -2.4806 -1.0167 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4091 -2.6697 -0.4843 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2084 -2.2079 -0.7122 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0353 -1.1296 -0.4619 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8396 0.0701 -1.1045 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6677 1.1420 -0.8507 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6859 0.9632 0.0618 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9247 -0.2132 0.7311 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0612 -1.2776 0.4448 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2490 -2.4917 1.0875 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4925 2.4575 -1.5212 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8949 3.4736 -0.5516 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0997 2.6590 3.1150 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9234 2.7848 1.8266 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8263 3.2560 -2.2493 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4480 2.5752 -1.7100 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8097 2.2651 -1.4702 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2017 0.5514 -2.5600 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2876 -1.7515 -1.6327 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6081 -0.6158 1.4378 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0324 -3.3947 -0.3439 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0072 -2.7183 1.0171 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0740 -4.0259 1.7664 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0766 -2.3647 2.3507 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6162 -2.7747 2.7518 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6010 -2.4424 1.8323 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0256 -2.3984 -2.0779 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2825 -2.7363 -1.1476 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0444 0.2166 -1.8198 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3454 1.8193 0.2631 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7232 -0.3420 1.4421 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8417 -3.3187 0.6714 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4875 2.8533 -1.8082 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8720 2.3818 -2.4316 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8982 4.4824 -0.9642 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5353 3.4420 0.3484 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 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 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 21 22 2 0 20 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 26 31 1 0 31 32 1 0 7 2 1 0 14 9 1 0 22 17 1 0 29 24 1 0 32 4 1 0 1 33 1 0 3 34 1 0 5 35 1 0 6 36 1 0 10 37 1 0 11 38 1 0 12 39 1 0 14 40 1 0 15 41 1 0 15 42 1 0 16 43 1 0 16 44 1 0 18 45 1 0 19 46 1 0 21 47 1 0 22 48 1 0 25 49 1 0 27 50 1 0 28 51 1 0 30 52 1 0 31 53 1 0 31 54 1 0 32 55 1 0 32 56 1 0 M END

Standard InCHIKey	UJIJNWKXNAZKOA-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C28H24O4/c29-25-14-10-22-7-6-21-11-15-27(26(30)17-21)32-24-3-1-2-20(16-24)5-4-19-8-12-23(13-9-19)31-28(25)18-22/h1-3,8-18,29-30H,4-7H2
SMILES	Oc1cc2ccc1Oc1cccc(c1)CCc1ccc(cc1)Oc1cc(ccc1O)CC2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	424.17	Volume:	453.585 ? Van der Waals volume.
Dense:	0.935	LogP:	4.309 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.505 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.79 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	34.0
TPSA:	58.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	8.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.335	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.03	Fsp³:	0.143
MCE-18:	56.25 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.458 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.255 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.795 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.641	Promiscuous compounds:	0.145

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.799	MDCK Permeability:	-4.788
Pgp-inhibitor:	0.945	Pgp-substrate:	0.049
PAMPA:	0.033 ? 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%):	0.543	30% Bioavailability (F30%):	0.73
50% Bioavailability (F50%):	0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.568	MRP1:	0.716
Plasma Protein Binding (PPB):	98.836%	Volume Distribution (VD):	0.34
Fu:	0.381% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.927
OATP1B3 inhibitor:	0.981	BCRP inhibitor:	0.11
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.474	CYP1A2-substrate:	0.986
CYP2C19-inhibitor:	0.344	CYP2C19-substrate:	0.994
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.026
CYP2D6-inhibitor:	0.987	CYP2D6-substrate:	0.38
CYP3A4-inhibitor:	0.747	CYP3A4-substrate:	0.996
CYP2B6-substrate:	0.328	CYP2C8-inhibitor:	0.999
HLM stability:	0.994 ? 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):

8.559

Half-life (T1/2):

0.685

ADMET: Toxicity

hERG Blockers:	0.542	hERG Blockers (10um):	0.834
Human Hepatotoxicity (H-HT):	0.472	Drug-induced Liver Injury (DILI):	0.202
AMES Toxicity:	0.501	Rat Oral Acute Toxicity:	0.395
Maximum Recommended Daily Dose:	0.517	Skin Sensitization:	0.672
Carcinogencity:	0.542	Eye Corrosion:	0.001
Eye Irritation:	0.767	Respiratory Toxicity:	0.485
Drug-induced Neurotoxicity:	0.372	Ototoxicity:	0.307
Hematotoxicity:	0.162	Drug-induced Nephrotoxicity:	0.211
Genotoxicity:	0.268	RPMI-8226 Immunitoxicity:	0.056
A549 Cytotoxicity:	0.57	Hek293 Cytotoxicity:	0.76
BCF:	1.773 ? 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:	4.924 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.597 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.281 ? 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
NPO10949	Riccardia multifida	Species	Aneuraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21625478]
NPO10949	Riccardia multifida	Species	Aneuraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO52507	Asterella angusta	Genus	Aytoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10949	Riccardia multifida	Species	Aneuraceae	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

Activity Type	# Activity
MIC	2

Activity Type	# Activity
Organism	2

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
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	0.25	ug	PMID[29019405]
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	16.0	ug.mL-1	PMID[29019405]

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 NPC599909 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	26364
0.1-0.2	20422
0.2-0.3	2788
0.3-0.4	216
0.4-0.5	42
0.5-0.6	11
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC604545
0.7843	Intermediate Similarity	NPC474134
0.7708	Intermediate Similarity	NPC5948
0.7692	Intermediate Similarity	NPC601463
0.7358	Intermediate Similarity	NPC304630
0.7273	Intermediate Similarity	NPC226193
0.7273	Intermediate Similarity	NPC601081
0.7222	Intermediate Similarity	NPC134431
0.7222	Intermediate Similarity	NPC156854
0.7037	Intermediate Similarity	NPC17837
0.6964	Remote Similarity	NPC610261
0.6842	Remote Similarity	NPC606874
0.6667	Remote Similarity	NPC474390
0.625	Remote Similarity	NPC86947
0.6129	Remote Similarity	NPC210655
0.5902	Remote Similarity	NPC66840
0.5873	Remote Similarity	NPC601376
0.5738	Remote Similarity	NPC256307
0.5738	Remote Similarity	NPC73656
0.5645	Remote Similarity	NPC606516
0.5636	Remote Similarity	NPC131128
0.5469	Remote Similarity	NPC141023
0.5397	Remote Similarity	NPC599974
0.5306	Remote Similarity	NPC607269
0.5088	Remote Similarity	NPC485986
0.5079	Remote Similarity	NPC483726

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC599909 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4222
0.1-0.2	4757
0.2-0.3	162
0.3-0.4	9
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