NPASS Compound

Natural Product: NPC204812

Natural Product ID	NPC204812
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Jaborosalactone
IUPAC Name	n.a.
Synonyms	Jaborosalactone 38
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL224127
PubChem CID	16680130
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones

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 71 77 0 0 0 0 0 0 0 0999 V2000 5.6718 2.7547 0.2068 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1266 1.4851 -0.3087 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5557 0.3464 0.1738 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5990 0.2645 1.2497 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0063 -0.9074 -0.3385 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3699 -2.0140 0.0750 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0349 -0.8487 -1.3321 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2290 0.3186 -1.4582 C 0 0 2 0 0 0 0 0 0 0 0 0 4.1077 1.5162 -1.3655 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1569 0.2643 -0.4050 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2443 1.4472 -0.4337 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0191 1.2488 0.0353 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1611 0.2339 0.9670 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1383 -1.0582 0.2638 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4354 -1.0546 -0.4693 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2752 -2.0243 0.1020 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1572 -1.5068 -1.8922 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2563 -2.1171 -1.7798 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8561 -1.1238 -0.8850 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2140 -1.3603 -0.3575 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5504 -0.0376 0.3560 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5952 0.2682 1.4517 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9901 0.0165 0.6868 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5442 -1.3088 1.2283 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3266 1.0319 1.6841 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7621 0.9947 2.8020 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2909 2.0982 1.4572 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5940 2.4422 0.2200 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9499 1.7405 -0.8887 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7138 0.2732 -0.6452 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1783 -0.5014 -1.6758 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2318 -1.6162 -1.4382 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5478 -0.6965 -1.1308 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0231 -2.2403 1.1873 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6977 0.4702 2.0328 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5486 2.8527 1.3091 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1326 3.6330 -0.2328 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7449 2.9091 -0.0910 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7491 1.2430 1.7430 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3001 -0.5178 1.9846 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5474 -0.0341 0.7604 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8173 0.2834 -2.4899 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6843 1.5561 -2.3394 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5458 2.4771 -1.3623 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6833 0.2801 0.5839 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6987 2.2981 0.1436 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1518 1.8559 -1.4827 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5376 -2.7251 -0.5455 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8801 -2.2217 -2.2752 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9944 -0.6226 -2.5770 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6614 -2.1463 -2.8102 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2023 -3.1387 -1.4143 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8278 -0.1251 -1.3696 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2306 -2.2132 0.3265 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3594 0.7364 -0.4489 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7596 1.3585 1.7125 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7625 -0.3133 2.3634 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7458 -1.9425 1.6453 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2478 -1.1284 2.0939 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1858 -1.8176 0.4760 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7758 2.6272 2.2810 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3183 3.2426 0.0504 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9465 2.2125 -1.0738 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4968 1.8167 -1.8459 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3308 -0.2042 -2.7536 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6272 -1.8047 -2.3768 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7852 -2.5734 -1.3011 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9795 -2.3434 1.7265 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1582 -3.1716 0.6430 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7968 -2.0798 1.9112 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1760 0.9423 2.7266 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 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 1 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 23 24 1 1 23 25 1 0 25 26 2 0 25 27 1 0 27 28 2 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 31 33 1 0 14 34 1 1 13 35 1 1 9 2 1 0 15 10 1 0 32 20 1 0 22 13 1 0 30 23 1 0 19 14 1 0 30 33 1 1 1 36 1 0 1 37 1 0 1 38 1 0 4 39 1 0 4 40 1 0 4 41 1 0 8 42 1 6 9 43 1 0 9 44 1 0 10 45 1 1 11 46 1 0 11 47 1 0 16 48 1 0 17 49 1 0 17 50 1 0 18 51 1 0 18 52 1 0 19 53 1 6 20 54 1 1 21 55 1 6 22 56 1 0 22 57 1 0 24 58 1 0 24 59 1 0 24 60 1 0 27 61 1 0 28 62 1 0 29 63 1 0 29 64 1 0 31 65 1 6 32 66 1 0 32 67 1 0 34 68 1 0 34 69 1 0 34 70 1 0 35 71 1 0 M END

Standard InCHIKey	JHGQZOZYOJZSAH-HTNNWKMKSA-N
Standard InCHI	InChI=1S/C28H36O7/c1-14-10-20(34-23(30)15(14)2)19-13-33-28(32)12-18-16(17-7-9-26(19,31)25(17,28)4)11-22-27(35-22)8-5-6-21(29)24(18,27)3/h5-6,16-20,22,31-32H,7-13H2,1-4H3/t16-,17-,18-,19+,20+,22+,24-,25-,26+,27+,28-/m0/s1
SMILES	CC1=C(C)C(=O)O[C@H](C1)[C@H]1CO[C@@]2([C@@]3([C@@]1(O)CC[C@H]3[C@H]1[C@H](C2)[C@@]2(C)C(=O)C=CC[C@]32[C@@H](C1)O3)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	484.25	Volume:	483.935 ? Van der Waals volume.
Dense:	1.001	LogP:	1.561 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.953 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.974 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	34.0
TPSA:	105.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	7.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.436	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.155	Fsp³:	0.786
MCE-18:	171.12 ? 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:	0.316	Fluc inhibitor:	0.024 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? 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:	0.233	Promiscuous compounds:	0.975

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.952	MDCK Permeability:	-4.856
Pgp-inhibitor:	0.005	Pgp-substrate:	0.876
PAMPA:	0.997 ? 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):	0.003
20% Bioavailability (F20%):	0.141	30% Bioavailability (F30%):	0.201
50% Bioavailability (F50%):	0.77

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.954
Plasma Protein Binding (PPB):	79.287%	Volume Distribution (VD):	0.028
Fu:	20.579% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.974	BCRP inhibitor:	0.015
BSEP inhibitor:	0.957

ADMET: Metabolism

CYP1A2-inhibitor:	0.418	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.467	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.5	CYP3A4-substrate:	0.052
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.123
HLM stability:	0.101 ? 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):

6.347

Half-life (T1/2):

2.414

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.334
Human Hepatotoxicity (H-HT):	0.476	Drug-induced Liver Injury (DILI):	0.235
AMES Toxicity:	0.448	Rat Oral Acute Toxicity:	0.618
Maximum Recommended Daily Dose:	0.909	Skin Sensitization:	0.997
Carcinogencity:	0.407	Eye Corrosion:	0.02
Eye Irritation:	0.603	Respiratory Toxicity:	0.568
Drug-induced Neurotoxicity:	0.081	Ototoxicity:	0.471
Hematotoxicity:	0.11	Drug-induced Nephrotoxicity:	0.548
Genotoxicity:	0.812	RPMI-8226 Immunitoxicity:	0.165
A549 Cytotoxicity:	0.005	Hek293 Cytotoxicity:	0.314
BCF:	0.855 ? 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:	3.575 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.341 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.596 ? 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
NPO40172	Jaborosa caulescens var. bipinnatifida	Strain	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17428092]
NPO40171	Jaborosa caulescens var. caulescens	Strain	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17428092]
NPO10136	Miconia fallax	Species	Melastomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9595	Penicillium parvum	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7215	Astragalus adscendens	Species	Fabaceae	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
Activity	6
GI50	5

Activity Type	# Activity
Cell line	4
Organism	6
Non-molecular	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
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	=	3400.0	nM	PMID[20438092]
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	2900.0	nM	PMID[20438092]
NPT396	Cell line	T47D	Homo sapiens	GI50	=	4100.0	nM	PMID[20438092]
NPT134	Cell line	SK-BR-3	Homo sapiens	GI50	=	2600.0	nM	PMID[20438092]
NPT364	Organism	Lactuca sativa	Lactuca sativa	Activity	=	-1.6	%	PMID[17428092]
NPT364	Organism	Lactuca sativa	Lactuca sativa	Activity	=	-46.2	%	PMID[17428092]
NPT364	Organism	Lactuca sativa	Lactuca sativa	Activity	=	-58.6	%	PMID[17428092]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	2800.0	nM	PMID[20438092]
NPT1866	Organism	Avena sativa	Avena sativa	Activity	=	-13.9	%	PMID[17428092]
NPT1866	Organism	Avena sativa	Avena sativa	Activity	=	2.4	%	PMID[17428092]
NPT1866	Organism	Avena sativa	Avena sativa	Activity	=	-36.5	%	PMID[17428092]

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 NPC204812 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	16152
0.1-0.2	31582
0.2-0.3	1940
0.3-0.4	140
0.4-0.5	29
0.5-0.6	10
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
0.7595	Intermediate Similarity	NPC113448
0.6786	Remote Similarity	NPC32868
0.675	Remote Similarity	NPC287423
0.6707	Remote Similarity	NPC241456
0.5581	Remote Similarity	NPC305496
0.5581	Remote Similarity	NPC484712
0.5517	Remote Similarity	NPC484714
0.5517	Remote Similarity	NPC166213
0.5517	Remote Similarity	NPC605398
0.5476	Remote Similarity	NPC122056
0.5393	Remote Similarity	NPC164523
0.5294	Remote Similarity	NPC158285
0.5169	Remote Similarity	NPC484736
0.5055	Remote Similarity	NPC55621

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC204812 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6040
0.1-0.2	3003
0.2-0.3	106
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