NPASS Compound

Natural Product: NPC220688

Natural Product ID	NPC220688
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	WAGHNVSMIQWJHO-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000025] Phenanthrenes and derivatives [CHEMONTID:0003007] Phenanthrols

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 -0.2048 -3.6564 -2.6366 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0720 -2.3903 -2.0609 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0588 -1.7485 -1.3248 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2714 -2.3474 -1.1127 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2494 -1.6727 -0.3639 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9764 -0.4310 0.1404 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9444 0.2426 0.8825 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1795 -0.2919 1.1365 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0789 0.4619 1.8896 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7507 1.7077 2.3709 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5058 2.2342 2.1088 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6102 1.5081 1.3710 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3770 2.0869 1.1400 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4368 1.4196 0.4128 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7191 0.1674 -0.0909 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7624 -0.5075 -0.8306 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5366 0.1320 -1.0630 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5969 -0.0804 -0.1749 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2834 -0.9676 0.9462 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3650 -1.2312 1.9046 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6336 -0.5642 1.6300 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6469 -0.8218 2.5563 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8885 -0.2544 2.4084 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1199 0.5684 1.3390 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1239 0.8505 0.3865 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8979 0.2740 0.5561 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8238 0.5338 -0.4029 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0150 1.3476 -1.4867 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9537 1.5444 -2.3527 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7315 0.9483 -2.1487 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3264 1.1575 -3.0311 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1411 1.9856 -4.1392 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1801 1.9847 -1.7815 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9203 -0.4991 3.3260 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6314 2.4722 3.1215 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4569 -2.3053 -0.1706 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8056 -4.1216 -2.6538 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8662 -4.3397 -2.0622 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6040 -3.5240 -3.6757 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5385 -3.3215 -1.4860 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5028 -1.2368 0.8029 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0431 0.0548 2.0930 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2333 3.2256 2.4871 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1372 3.0767 1.5312 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4441 1.8282 0.1983 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4445 -0.4711 1.5210 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8107 -1.9102 0.5651 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5802 -2.3419 1.8880 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0974 -1.0110 2.9618 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5004 -1.4663 3.4128 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0814 1.0216 1.2043 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3508 1.4917 -0.4212 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1045 2.1988 -3.2259 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1339 2.1177 -4.6299 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5601 1.5859 -4.8884 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1862 3.0051 -3.8152 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4666 2.1047 -2.7565 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5738 0.2740 3.4800 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1075 1.9755 3.8832 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9152 -2.8820 -0.8692 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 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 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 1 0 28 33 1 0 23 34 1 0 10 35 1 0 5 36 1 0 16 3 1 0 30 17 1 0 15 6 1 0 27 18 1 0 12 7 1 0 26 21 1 0 1 37 1 0 1 38 1 0 1 39 1 0 4 40 1 0 8 41 1 0 9 42 1 0 11 43 1 0 13 44 1 0 14 45 1 0 19 46 1 0 19 47 1 0 20 48 1 0 20 49 1 0 22 50 1 0 24 51 1 0 25 52 1 0 29 53 1 0 32 54 1 0 32 55 1 0 32 56 1 0 33 57 1 0 34 58 1 0 35 59 1 0 36 60 1 0 M END

Standard InCHIKey	WAGHNVSMIQWJHO-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C30H24O6/c1-35-25-13-23(33)27-19-9-5-17(31)11-15(19)3-7-21(27)29(25)30-22-8-4-16-12-18(32)6-10-20(16)28(22)24(34)14-26(30)36-2/h3,5-7,9-14,31-34H,4,8H2,1-2H3
SMILES	COc1cc(c2c3ccc(cc3ccc2c1c1c2CCc3cc(ccc3-c2c(cc1OC)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	480.16	Volume:	494.565 ? Van der Waals volume.
Dense:	0.971	LogP:	4.21 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.418 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.773 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	32.0
TPSA:	99.38 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.227	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.906	Fsp³:	0.133
MCE-18:	72.0 ? 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:	0.999	Fluc inhibitor:	0.508 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.583 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.714 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.297	Promiscuous compounds:	0.15

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.94	MDCK Permeability:	-4.79
Pgp-inhibitor:	0.007	Pgp-substrate:	0.399
PAMPA:	0.143 ? 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):	0.01
20% Bioavailability (F20%):	0.425	30% Bioavailability (F30%):	0.712
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.014	MRP1:	0.622
Plasma Protein Binding (PPB):	94.725%	Volume Distribution (VD):	0.35
Fu:	8.061% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.702
BSEP inhibitor:	0.407

ADMET: Metabolism

CYP1A2-inhibitor:	0.997	CYP1A2-substrate:	0.356
CYP2C19-inhibitor:	0.978	CYP2C19-substrate:	0.845
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.162
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.956
CYP3A4-inhibitor:	0.894	CYP3A4-substrate:	0.988
CYP2B6-substrate:	0.636	CYP2C8-inhibitor:	0.999
HLM stability:	0.981 ? 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):

1.535

Half-life (T1/2):

1.973

ADMET: Toxicity

hERG Blockers:	0.428	hERG Blockers (10um):	0.7
Human Hepatotoxicity (H-HT):	0.812	Drug-induced Liver Injury (DILI):	0.742
AMES Toxicity:	0.921	Rat Oral Acute Toxicity:	0.712
Maximum Recommended Daily Dose:	0.973	Skin Sensitization:	0.893
Carcinogencity:	0.906	Eye Corrosion:	0.0
Eye Irritation:	0.643	Respiratory Toxicity:	0.991
Drug-induced Neurotoxicity:	0.682	Ototoxicity:	0.813
Hematotoxicity:	0.41	Drug-induced Nephrotoxicity:	0.619
Genotoxicity:	0.972	RPMI-8226 Immunitoxicity:	0.167
A549 Cytotoxicity:	0.94	Hek293 Cytotoxicity:	0.958
BCF:	1.563 ? 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:	5.063 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.699 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.455 ? 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
NPO13319	Isodon lungshengensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10425112]
NPO11893	Telesto riisei	Species	Telestidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7857405]
NPO13086	Streptomyces carzinostaticus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26125	Pseudomonas corrugata	Species	Pseudomonadaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13319	Isodon lungshengensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO445	Desmarestia aculeata	Species	Desmarestiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14620	Sedum alfredi	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13319	Isodon lungshengensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13319	Isodon lungshengensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16226	Prinsepia utilis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12597	Eria barbata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7186	Hypogymnia enteromorpha	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14509	Stevia seleriana	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13319	Isodon lungshengensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12919	Clibadium glabrescens	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO445	Desmarestia aculeata	Species	Desmarestiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13511	Monopteryx inpae	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6224	Grindelia boliviana	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13913	Ravensara aromatica	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3644	Climacoptera lanata	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14620	Sedum alfredi	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13086	Streptomyces carzinostaticus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO26125	Pseudomonas corrugata	Species	Pseudomonadaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO11893	Telesto riisei	Species	Telestidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8734	Centaurea pabotii	Species	Asteraceae	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
IC50	2

Activity Type	# Activity
Cell line	1
No target	1

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
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	7.3	ug.mL-1	PMID[29280630]
NPT28833	No target	No relevant target	n.a.	IC50	=	15.1	ug.mL-1	PMID[29280630]

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 NPC220688 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	27916
0.1-0.2	20878
0.2-0.3	992
0.3-0.4	50
0.4-0.5	11
0.5-0.6	6
0.6-0.7	3
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	Natural Product ID
0.6623	Remote Similarity	NPC206525
0.6364	Remote Similarity	NPC6030
0.6154	Remote Similarity	NPC294436
0.5846	Remote Similarity	NPC227509
0.5672	Remote Similarity	NPC258780
0.5542	Remote Similarity	NPC472648
0.5333	Remote Similarity	NPC58963
0.5135	Remote Similarity	NPC478417
0.5067	Remote Similarity	NPC191462

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC220688 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5280
0.1-0.2	3858
0.2-0.3	12
0.3-0.4	0
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