NPASS Compound

Natural Product: NPC482235

Natural Product ID	NPC482235
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IMQVWZKEFSFWCH-FRTLHQRBSA-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]

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 77 80 0 0 0 0 0 0 0 0999 V2000 7.8216 0.6636 -0.1899 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7910 -0.6992 0.3899 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7436 -1.2406 0.9628 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8137 -2.6182 1.5155 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4920 -0.4649 1.0519 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5064 -0.9904 1.5985 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3713 0.8006 0.5614 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2841 1.6589 0.5614 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1128 1.0497 -0.1927 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4114 0.7079 -1.6146 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0974 0.3580 0.6394 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5183 -0.8886 0.0917 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0209 -1.0128 0.4487 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1099 -0.4508 1.8128 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7229 -0.4422 -0.6679 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1099 -1.5987 -1.5714 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3763 -1.9449 -1.3206 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0807 -3.0359 -2.0184 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9001 -1.0309 -0.2388 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0500 0.1696 -0.4957 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2363 1.2850 0.4171 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4087 2.4648 0.2066 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3473 2.7390 -0.5242 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7052 1.7438 -0.9575 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7370 1.6334 0.0859 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1176 0.5035 -1.4430 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3147 0.1809 -2.5915 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8859 3.6493 1.0208 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5763 1.7397 0.2214 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4289 0.6317 -1.7884 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2772 -0.8420 -0.3253 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2017 -1.1947 0.6121 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8018 -1.7408 1.6656 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6104 -0.9323 0.3704 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0757 -0.3735 -0.7097 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1716 0.0423 -1.7936 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5869 -1.3274 1.4249 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6225 1.3892 0.6426 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8406 0.9154 -0.5583 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0964 0.8105 -1.0032 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7000 -1.3135 0.3460 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0070 -2.5969 2.6162 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5634 -3.2428 0.9874 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8194 -3.0922 1.3027 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0083 1.8499 1.6275 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5778 2.6340 0.1401 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8356 1.2388 -2.3744 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3553 -0.4030 -1.7338 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4796 0.9538 -1.8196 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1928 0.3268 1.7668 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0800 -1.7512 0.5601 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5911 -1.0440 -0.9841 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1352 -2.1297 0.5522 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0223 -0.8245 2.3657 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7267 -0.9235 2.4207 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0602 0.6227 1.9126 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4045 -2.0137 -2.2784 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1907 -2.8270 -2.0448 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8622 -4.0316 -1.6273 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7729 -3.0050 -3.0905 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6634 -1.5325 0.7211 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2601 1.0278 1.5169 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2551 3.7631 -0.8169 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1829 2.2601 -1.8412 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7960 2.5320 0.7580 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9453 3.8645 0.7771 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2270 4.5166 0.8978 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8088 3.3237 2.0794 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5703 2.3013 -0.5766 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7730 1.2737 -2.1295 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1605 -0.2103 -0.8127 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7789 0.4301 -2.6602 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4799 0.8417 -1.5234 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6380 -0.8498 -2.2184 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9667 -2.3450 1.2397 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4518 -0.6354 1.4484 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0695 -1.2973 2.4100 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 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 15 1 0 15 16 1 6 16 17 2 0 17 18 1 0 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 24 26 1 0 26 27 2 0 22 28 1 0 21 29 1 0 20 30 1 6 19 31 1 0 31 32 1 0 32 33 2 0 32 34 1 0 34 35 2 0 35 36 1 0 34 37 1 0 25 9 1 0 25 11 1 0 26 15 1 0 20 15 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 0 4 42 1 0 4 43 1 0 4 44 1 0 8 45 1 0 8 46 1 0 10 47 1 0 10 48 1 0 10 49 1 0 11 50 1 1 12 51 1 0 12 52 1 0 13 53 1 1 14 54 1 0 14 55 1 0 14 56 1 0 16 57 1 0 18 58 1 0 18 59 1 0 18 60 1 0 19 61 1 1 21 62 1 1 23 63 1 0 24 64 1 6 25 65 1 1 28 66 1 0 28 67 1 0 28 68 1 0 29 69 1 0 30 70 1 0 35 71 1 0 36 72 1 0 36 73 1 0 36 74 1 0 37 75 1 0 37 76 1 0 37 77 1 0 M END

Standard InCHIKey	IMQVWZKEFSFWCH-FRTLHQRBSA-N
Standard InCHI	InChI=1S/C30H40O7/c1-9-15(3)26(33)36-14-28(8)21-12-19(7)29-13-18(6)25(37-27(34)16(4)10-2)30(29,35)23(31)17(5)11-20(22(21)28)24(29)32/h9-11,13,19-23,25,31,35H,12,14H2,1-8H3/b15-9-,16-10-/t19-,20+,21-,22+,23-,25+,28?,29-,30+/m1/s1
SMILES	C/C=C(/C)C(=O)OCC1(C)[C@@H]2C[C@@H](C)[C@]34C=C(C)[C@@H]([C@]4([C@@H](C(=C[C@@H]([C@H]12)C3=O)C)O)O)OC(=O)/C(=CC)/C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	512.28	Volume:	536.287 ? Van der Waals volume.
Dense:	0.955	LogP:	3.496 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.328 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.696 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	23.0
TPSA:	110.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.327	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.529	Fsp³:	0.633
MCE-18:	115.878 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.422	Fluc inhibitor:	0.015 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.06 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.243	Promiscuous compounds:	0.397

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.89	MDCK Permeability:	-4.679
Pgp-inhibitor:	0.035	Pgp-substrate:	0.28
PAMPA:	0.839 ? 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):	0.146
20% Bioavailability (F20%):	0.992	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.287	MRP1:	0.982
Plasma Protein Binding (PPB):	94.039%	Volume Distribution (VD):	0.268
Fu:	6.631% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.963	BCRP inhibitor:	0.002
BSEP inhibitor:	0.884

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.006
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.523
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.503
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.887 ? 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):

10.133

Half-life (T1/2):

1.131

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.257
Human Hepatotoxicity (H-HT):	0.43	Drug-induced Liver Injury (DILI):	0.304
AMES Toxicity:	0.524	Rat Oral Acute Toxicity:	0.463
Maximum Recommended Daily Dose:	0.662	Skin Sensitization:	0.982
Carcinogencity:	0.921	Eye Corrosion:	0.076
Eye Irritation:	0.77	Respiratory Toxicity:	0.361
Drug-induced Neurotoxicity:	0.193	Ototoxicity:	0.4
Hematotoxicity:	0.149	Drug-induced Nephrotoxicity:	0.783
Genotoxicity:	0.928	RPMI-8226 Immunitoxicity:	0.127
A549 Cytotoxicity:	0.049	Hek293 Cytotoxicity:	0.292
BCF:	1.613 ? 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:	4.581 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.257 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.894 ? 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
NPO40125	Euphorbia dulcis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30411614]

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
Inhibition	4
IC50	1

Activity Type	# Activity
Protein complex	3
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT98	Individual protein	HERG	Homo sapiens	Inhibition	=	11.2	%	PMID[30411614]
NPT98	Individual protein	HERG	Homo sapiens	Inhibition	=	55.4	%	PMID[30411614]
NPT4639	Protein complex	Kir3.1/Kir3.4	Homo sapiens	Inhibition	=	43.9	%	PMID[30411614]
NPT4639	Protein complex	Kir3.1/Kir3.4	Homo sapiens	Inhibition	=	80.4	%	PMID[30411614]
NPT4639	Protein complex	Kir3.1/Kir3.4	Homo sapiens	IC50	=	1450.0	nM	PMID[30411614]

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 NPC482235 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	17666
0.1-0.2	28840
0.2-0.3	3280
0.3-0.4	38
0.4-0.5	17
0.5-0.6	7
0.6-0.7	2
0.7-0.8	0
0.8-0.85	3
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	NPC479252
0.8182	Intermediate Similarity	NPC482236
0.8033	Intermediate Similarity	NPC482234
0.8033	Intermediate Similarity	NPC303053
0.7397	Intermediate Similarity	NPC479253
0.7	Intermediate Similarity	NPC607208
0.6716	Remote Similarity	NPC257240
0.6515	Remote Similarity	NPC600642
0.5733	Remote Similarity	NPC47951
0.5395	Remote Similarity	NPC609657
0.5342	Remote Similarity	NPC607683
0.527	Remote Similarity	NPC308191
0.527	Remote Similarity	NPC38423
0.5062	Remote Similarity	NPC482242
0.5062	Remote Similarity	NPC482243

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC482235 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6525
0.1-0.2	2540
0.2-0.3	84
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
0.6-0.7	1
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
0.6716	Remote Similarity	NPD6371	Phase 4

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