NPASS Compound

Natural Product: NPC183540

Natural Product ID	NPC183540
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IZHBNHCRPMQEPI-ZEUFARPOSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL516716
PubChem CID	24812993
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002875] Tigliane and ingenane diterpenoids [CHEMONTID:0002906] Phorbol esters

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 70 74 0 0 0 0 0 0 0 0999 V2000 0.0308 -5.5722 -0.8830 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1096 -4.1004 -0.6424 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7712 -3.2323 -1.1122 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4259 -1.8734 -0.7100 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6486 -1.9631 0.3146 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8439 -1.0757 -0.0381 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4246 0.1996 -0.6486 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2118 0.7965 -0.5593 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9819 0.3194 0.1707 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0559 1.3705 0.2641 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7470 1.6692 1.5211 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5990 0.9086 2.7914 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1519 3.1351 1.7499 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4296 0.9579 0.3107 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7458 -0.4840 0.5178 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5762 -1.4206 0.5681 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1341 -2.8038 0.3469 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5519 -0.9597 -0.3860 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1792 -0.6575 -1.6170 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5330 1.7001 -0.1620 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7026 2.1214 -1.4546 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8170 1.8350 -2.2919 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9223 2.8995 -1.8229 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3949 0.9215 -1.4734 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5557 1.3815 -0.9649 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6435 0.7776 -0.4623 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7058 -0.4533 -0.4159 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8111 1.5155 0.0567 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8867 0.8236 0.5551 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9973 1.4964 1.0492 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0585 2.8765 1.0566 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9779 3.5742 0.5559 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8709 2.8930 0.0636 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1259 -3.3810 0.1179 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2040 -3.8021 0.5510 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2665 -1.8870 1.6239 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0125 -5.9264 -0.9695 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5025 -6.1539 -0.0782 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5465 -5.8605 -1.8262 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6196 -3.5143 -1.7117 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0695 -1.4100 -1.6248 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4651 -1.6559 -0.7871 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4298 -1.0021 0.8812 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1433 1.7390 -1.1016 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6336 0.1740 1.2291 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8247 2.2579 -0.3897 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7725 1.5537 3.7060 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3751 0.0990 2.9275 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6278 0.4444 2.9746 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1963 3.1764 2.0734 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0729 3.6690 0.7877 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4241 3.5356 2.4622 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4513 -0.6412 1.3693 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3516 -0.8017 -0.3846 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1270 -1.4370 1.5845 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9647 -2.8935 1.1169 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6453 -2.9406 -0.6064 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4350 -3.6096 0.6428 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5067 -0.2591 -2.2446 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7591 3.3807 -2.8013 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0949 3.7102 -1.0834 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8025 2.2293 -1.7937 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5816 0.3122 -2.4316 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8527 1.8215 -1.9267 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9291 -0.2549 0.5903 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8556 0.9598 1.4467 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9117 3.4248 1.4357 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9630 4.6579 0.5332 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0388 3.4622 -0.3225 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0353 -2.7534 1.9767 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 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 0 11 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 16 18 1 0 18 19 1 6 14 20 1 6 20 21 1 0 21 22 2 0 21 23 1 0 7 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 5 34 1 0 34 35 2 0 5 36 1 1 34 2 1 0 18 4 1 0 33 28 1 0 18 9 1 0 14 10 1 0 1 37 1 0 1 38 1 0 1 39 1 0 3 40 1 0 4 41 1 6 6 42 1 0 6 43 1 0 8 44 1 0 9 45 1 1 10 46 1 6 12 47 1 0 12 48 1 0 12 49 1 0 13 50 1 0 13 51 1 0 13 52 1 0 15 53 1 0 15 54 1 0 16 55 1 1 17 56 1 0 17 57 1 0 17 58 1 0 19 59 1 0 23 60 1 0 23 61 1 0 23 62 1 0 24 63 1 0 24 64 1 0 29 65 1 0 30 66 1 0 31 67 1 0 32 68 1 0 33 69 1 0 36 70 1 0 M END

Standard InCHIKey	IZHBNHCRPMQEPI-ZEUFARPOSA-N
Standard InCHI	InChI=1S/C29H34O7/c1-16-11-22-27(33,24(16)31)14-19(15-35-25(32)20-9-7-6-8-10-20)12-21-23-26(4,5)28(23,36-18(3)30)13-17(2)29(21,22)34/h6-12,17,21-23,33-34H,13-15H2,1-5H3/t17-,21+,22-,23-,27-,28+,29-/m1/s1
SMILES	CC1=C[C@@H]2[C@](CC(=C[C@H]3[C@@H]4C(C)(C)[C@@]4(C[C@@H](C)[C@]23O)OC(=O)C)COC(=O)c2ccccc2)(C1=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	494.23	Volume:	507.798 ? Van der Waals volume.
Dense:	0.973	LogP:	2.868 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.078 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.16 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	27.0
TPSA:	110.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.488	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.706	Fsp³:	0.552
MCE-18:	127.444 ? 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:	0.207	Fluc inhibitor:	0.029 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.048 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.131	Promiscuous compounds:	0.12

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.0	MDCK Permeability:	-4.561
Pgp-inhibitor:	0.801	Pgp-substrate:	0.328
PAMPA:	0.568 ? 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%):	0.336	30% Bioavailability (F30%):	0.627
50% Bioavailability (F50%):	0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.07	MRP1:	0.995
Plasma Protein Binding (PPB):	76.325%	Volume Distribution (VD):	0.036
Fu:	21.93% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.012
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.506
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.239
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.143
CYP3A4-inhibitor:	0.007	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

5.697

Half-life (T1/2):

0.728

ADMET: Toxicity

hERG Blockers:	0.118	hERG Blockers (10um):	0.439
Human Hepatotoxicity (H-HT):	0.149	Drug-induced Liver Injury (DILI):	0.5
AMES Toxicity:	0.189	Rat Oral Acute Toxicity:	0.173
Maximum Recommended Daily Dose:	0.61	Skin Sensitization:	0.953
Carcinogencity:	0.645	Eye Corrosion:	0.0
Eye Irritation:	0.464	Respiratory Toxicity:	0.26
Drug-induced Neurotoxicity:	0.14	Ototoxicity:	0.272
Hematotoxicity:	0.132	Drug-induced Nephrotoxicity:	0.327
Genotoxicity:	0.66	RPMI-8226 Immunitoxicity:	0.081
A549 Cytotoxicity:	0.126	Hek293 Cytotoxicity:	0.395
BCF:	1.024 ? 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:	3.816 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.505 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.964 ? 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
NPO422	Euphorbia cornigera	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17512094]
NPO422	Euphorbia cornigera	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19376614]
NPO422	Euphorbia cornigera	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO422	Euphorbia cornigera	Species	Euphorbiaceae	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	1

Activity Type	# Activity
Cell line	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
NPT91	Cell line	KB	Homo sapiens	IC50	=	8.2	ug.mL-1	DOI[10.1016/j.cropro.2006.02.001]

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 NPC183540 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	7384
0.1-0.2	39780
0.2-0.3	2212
0.3-0.4	405
0.4-0.5	37
0.5-0.6	20
0.6-0.7	15
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC159692
0.7313	Intermediate Similarity	NPC96739
0.7237	Intermediate Similarity	NPC602538
0.6806	Remote Similarity	NPC260786
0.6761	Remote Similarity	NPC174471
0.6757	Remote Similarity	NPC170212
0.6575	Remote Similarity	NPC474871
0.6329	Remote Similarity	NPC479000
0.6316	Remote Similarity	NPC17138
0.6316	Remote Similarity	NPC101825
0.6316	Remote Similarity	NPC215643
0.6316	Remote Similarity	NPC265499
0.6286	Remote Similarity	NPC153036
0.6286	Remote Similarity	NPC91189
0.6234	Remote Similarity	NPC221511
0.6087	Remote Similarity	NPC102367
0.6	Remote Similarity	NPC151216
0.6	Remote Similarity	NPC89227
0.5976	Remote Similarity	NPC222307
0.5914	Remote Similarity	NPC478683
0.5851	Remote Similarity	NPC478682
0.5733	Remote Similarity	NPC475937
0.5676	Remote Similarity	NPC158523
0.5526	Remote Similarity	NPC71889
0.5513	Remote Similarity	NPC485736
0.5513	Remote Similarity	NPC277477
0.5513	Remote Similarity	NPC479003
0.5513	Remote Similarity	NPC485735
0.5513	Remote Similarity	NPC485733
0.5422	Remote Similarity	NPC474937
0.5366	Remote Similarity	NPC475391
0.519	Remote Similarity	NPC478681
0.5185	Remote Similarity	NPC482454
0.5181	Remote Similarity	NPC485731
0.5181	Remote Similarity	NPC485732
0.5181	Remote Similarity	NPC482317
0.5114	Remote Similarity	NPC472398
0.5114	Remote Similarity	NPC600915

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC183540 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2946
0.1-0.2	6021
0.2-0.3	182
0.3-0.4	1
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