NPASS Compound

Natural Product: NPC274282

Natural Product ID	NPC274282
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BTCICADMSGBCKA-WVKQWSHJSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11753405
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001586] Biflavonoids and polyflavonoids

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 68 73 0 0 0 0 0 0 0 0999 V2000 -4.6326 3.2238 2.9900 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7272 1.8679 2.5464 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7447 1.4111 1.6593 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8104 0.1111 1.2157 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8347 -0.3289 0.3398 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8000 0.4440 -0.1204 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7547 1.7440 0.3380 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7246 2.2242 1.2248 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8055 -0.0575 -1.0659 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2936 -0.8997 -0.5730 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0567 -0.5317 0.6228 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2852 -0.3911 1.8754 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4672 -1.3076 2.2498 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3765 0.8070 2.7075 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2330 0.8401 3.9621 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1235 1.9927 4.7155 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5659 3.0981 4.2616 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1509 3.0244 3.0222 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0736 1.8861 2.2164 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6544 1.8100 0.9817 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0937 0.5564 0.4919 C 0 0 2 0 0 0 0 0 0 0 0 0 2.7828 0.6169 -0.8038 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8381 -0.2247 -1.0684 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4824 -0.1360 -2.2822 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1313 0.7562 -3.2633 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0778 1.5973 -3.0005 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4145 1.5170 -1.7696 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7721 0.8554 -4.4903 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8747 -0.0116 -4.7886 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6185 4.2068 5.0923 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9128 -0.2950 4.3714 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0882 -2.3496 -0.4658 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3702 -3.0261 0.4649 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9735 -2.9313 -1.4370 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0832 -4.2966 -1.5267 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9425 -4.8182 -2.4702 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6719 -3.9946 -3.3011 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5311 -2.6240 -3.1769 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6797 -2.0687 -2.2429 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5274 -0.7264 -2.1053 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5305 -4.5604 -4.2429 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3572 -5.1570 -0.6987 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4635 3.4444 3.6903 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6887 3.3044 3.5825 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6209 3.9259 2.1255 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6155 -0.5537 1.5498 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9118 -1.3726 0.0002 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9783 2.4281 0.0319 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6914 3.2473 1.5873 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3420 0.8118 -1.6372 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0613 -0.9266 -1.4325 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7072 -1.4674 0.8396 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6085 1.9800 5.6808 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6871 3.8738 2.6606 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9566 0.3044 1.2194 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1552 -0.9590 -0.3073 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3158 -0.7948 -2.5014 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7552 2.3223 -3.7363 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5848 2.1884 -1.5627 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5231 -1.0471 -4.5149 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1015 -0.0264 -5.8551 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7446 0.2284 -4.1403 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7506 4.1452 6.1007 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2575 -0.3056 5.3373 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0170 -5.9064 -2.5273 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1248 -1.9974 -3.8523 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2144 -5.1966 -4.9612 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7650 -5.5044 0.1668 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 6 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 25 28 1 0 28 29 1 0 17 30 1 0 15 31 1 0 10 32 1 0 32 33 2 0 32 34 1 0 34 35 2 0 35 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 39 40 1 0 37 41 1 0 35 42 1 0 8 3 1 0 40 9 1 0 21 11 1 0 27 22 1 0 39 34 1 0 19 14 1 0 1 43 1 0 1 44 1 0 1 45 1 0 4 46 1 0 5 47 1 0 7 48 1 0 8 49 1 0 9 50 1 6 10 51 1 6 11 52 1 1 16 53 1 0 18 54 1 0 21 55 1 1 23 56 1 0 24 57 1 0 26 58 1 0 27 59 1 0 29 60 1 0 29 61 1 0 29 62 1 0 30 63 1 0 31 64 1 0 36 65 1 0 38 66 1 0 41 67 1 0 42 68 1 0 M END

Standard InCHIKey	BTCICADMSGBCKA-WVKQWSHJSA-N
Standard InCHI	InChI=1S/C32H26O10/c1-39-19-7-3-15(4-8-19)31-27(29(37)25-21(35)11-17(33)13-23(25)41-31)28-30(38)26-22(36)12-18(34)14-24(26)42-32(28)16-5-9-20(40-2)10-6-16/h3-14,27-28,31-36H,1-2H3/t27-,28+,31-,32+
SMILES	COc1ccc(cc1)[C@H]1[C@@H]([C@@H]2C(=O)c3c(cc(cc3O[C@@H]2c2ccc(cc2)OC)O)O)C(=O)c2c(cc(cc2O1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	570.15	Volume:	561.681 ? Van der Waals volume.
Dense:	1.015	LogP:	3.714 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.425 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.024 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	36.0
TPSA:	151.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.255	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.004	Fsp³:	0.188
MCE-18:	115.579 ? 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:	0.985	Fluc inhibitor:	0.963 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.082 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.957 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.436	Promiscuous compounds:	0.233

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.346	MDCK Permeability:	-4.845
Pgp-inhibitor:	0.995	Pgp-substrate:	0.15
PAMPA:	0.034 ? 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):	0.016
20% Bioavailability (F20%):	0.005	30% Bioavailability (F30%):	0.99
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.729
Plasma Protein Binding (PPB):	97.498%	Volume Distribution (VD):	0.507
Fu:	2.167% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	1.0
BSEP inhibitor:	0.936

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.095
CYP2C19-inhibitor:	0.063	CYP2C19-substrate:	0.561
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.946
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.016
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.998 ? 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):

4.838

Half-life (T1/2):

1.673

ADMET: Toxicity

hERG Blockers:	0.21	hERG Blockers (10um):	0.609
Human Hepatotoxicity (H-HT):	0.623	Drug-induced Liver Injury (DILI):	0.904
AMES Toxicity:	0.789	Rat Oral Acute Toxicity:	0.416
Maximum Recommended Daily Dose:	0.759	Skin Sensitization:	0.483
Carcinogencity:	0.65	Eye Corrosion:	0.0
Eye Irritation:	0.939	Respiratory Toxicity:	0.893
Drug-induced Neurotoxicity:	0.132	Ototoxicity:	0.431
Hematotoxicity:	0.171	Drug-induced Nephrotoxicity:	0.579
Genotoxicity:	0.986	RPMI-8226 Immunitoxicity:	0.274
A549 Cytotoxicity:	0.718	Hek293 Cytotoxicity:	0.961
BCF:	1.553 ? 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:	4.699 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.6 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.813 ? 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
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	root	n.a.	PMID[15997133]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	root	n.a.	PMID[16141313]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	callus	n.a.	PMID[22368856]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23611151]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	roots	n.a.	n.a.	PMID[24931277]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26562066]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34770847]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	root	n.a.	Database[Article]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	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 NPC274282 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	24543
0.1-0.2	20574
0.2-0.3	4078
0.3-0.4	547
0.4-0.5	85
0.5-0.6	9
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
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	NPC287789
0.8431	Intermediate Similarity	NPC271741
0.7872	Intermediate Similarity	NPC201227
0.7872	Intermediate Similarity	NPC258474
0.7843	Intermediate Similarity	NPC484335
0.7255	Intermediate Similarity	NPC602118
0.6667	Remote Similarity	NPC484336
0.6667	Remote Similarity	NPC484337
0.6538	Remote Similarity	NPC274784
0.6538	Remote Similarity	NPC20709
0.6111	Remote Similarity	NPC44721
0.6111	Remote Similarity	NPC211466
0.6111	Remote Similarity	NPC605332
0.5965	Remote Similarity	NPC600886
0.5745	Remote Similarity	NPC212379
0.5345	Remote Similarity	NPC129853
0.5345	Remote Similarity	NPC76445
0.5345	Remote Similarity	NPC302950
0.5283	Remote Similarity	NPC603336
0.5273	Remote Similarity	NPC56031
0.5156	Remote Similarity	NPC108456
0.5088	Remote Similarity	NPC338131

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC274282 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4536
0.1-0.2	4459
0.2-0.3	139
0.3-0.4	13
0.4-0.5	0
0.5-0.6	1
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
0.5345	Remote Similarity	NPD1934	Phase 0

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