NPASS Compound

Natural Product: NPC250757

Natural Product ID	NPC250757
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Stellettin L
IUPAC Name	(2E,4E,6E,8E,10E)-10-[(3aS,5aR,7S,9aR,9bS)-7-hydroxy-3a,6,6,9a-tetramethyl-2-oxo-1,4,5,5a,7,8,9,9b-octahydrocyclopenta[a]naphthalen-3-ylidene]-2,6-dimethylundeca-2,4,6,8-tetraenoic acid
Synonyms	stellettin L
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL228656
PubChem CID	16756664
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 76 78 0 0 0 0 0 0 0 0999 V2000 4.7508 0.5287 -2.9256 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4015 -0.3885 -1.8432 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1429 -0.3835 -1.4329 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1287 0.4834 -2.0113 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8780 0.5057 -1.6229 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1665 1.3470 -2.1645 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3727 1.3464 -1.6536 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4431 2.1876 -2.1888 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4246 3.1360 -2.9795 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7432 1.6814 -1.5690 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1443 1.4229 -0.2161 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0502 1.0712 0.8801 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.4997 2.3939 1.5348 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3074 0.3453 0.5383 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7410 -0.6537 1.5729 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4247 -0.2665 2.9933 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9007 -0.2145 3.0941 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5398 -1.7082 3.3311 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4448 0.4420 4.3657 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2538 0.2260 1.8498 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9212 0.9132 1.9833 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1022 0.5576 0.7197 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9546 0.5897 -0.5283 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2163 -0.7850 -1.0771 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0723 0.8322 3.4691 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1114 2.2369 -3.3489 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3410 -1.2834 -1.2104 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6133 -1.3807 -1.5262 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5324 -2.2957 -0.8657 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8069 -2.3875 -1.1876 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3609 -1.5395 -2.2600 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6844 -3.3190 -0.4991 C 0 0 0 0 0 0 0 0 0 0 0 0 10.8984 -3.4139 -0.7977 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2309 -4.1536 0.5235 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7838 0.4083 -3.2723 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1058 0.2824 -3.7974 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5940 1.5768 -2.5908 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8613 -1.0467 -0.6391 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4455 1.1374 -2.7976 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6334 -0.1928 -0.8371 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0068 0.8040 -2.1470 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5216 2.4424 -1.5993 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6595 2.4315 0.0397 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0647 3.2787 0.9714 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1352 2.5247 2.5454 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5987 2.5631 1.3999 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1779 1.0678 0.4558 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3148 -0.1700 -0.4376 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8213 -0.8727 1.4124 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2082 -1.6061 1.3709 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8305 -1.1249 3.6131 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5591 -1.7679 3.8591 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4124 -2.1715 2.3200 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3388 -2.2146 3.9080 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6961 -0.1779 4.9471 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3429 0.4520 5.0537 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9618 1.4087 4.2719 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0400 -0.7064 1.2411 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0039 2.0169 2.0525 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4020 0.4842 2.8603 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7884 -0.4834 0.8913 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3017 1.3082 0.7009 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5921 -1.5155 -0.4780 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2496 -1.1088 -1.1092 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8263 -0.9385 -2.1215 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7452 0.6832 4.1600 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0105 1.8876 -3.8790 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1373 3.2875 -3.0419 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7361 2.0451 -4.0802 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9971 -1.9364 -0.4118 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0278 -0.7660 -2.3092 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1514 -2.9223 -0.0798 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9960 -1.9576 -3.2335 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4567 -1.5467 -2.2952 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0573 -0.4668 -2.1578 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9194 -4.4709 1.2185 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 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 1 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 1 0 17 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 6 16 25 1 0 6 26 1 0 2 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 30 32 1 0 32 33 2 0 32 34 1 0 23 7 1 0 23 11 1 0 20 12 1 0 1 35 1 0 1 36 1 0 1 37 1 0 3 38 1 0 4 39 1 0 5 40 1 0 10 41 1 0 10 42 1 0 11 43 1 1 13 44 1 0 13 45 1 0 13 46 1 0 14 47 1 0 14 48 1 0 15 49 1 0 15 50 1 0 16 51 1 1 18 52 1 0 18 53 1 0 18 54 1 0 19 55 1 0 19 56 1 0 19 57 1 0 20 58 1 6 21 59 1 0 21 60 1 0 22 61 1 0 22 62 1 0 24 63 1 0 24 64 1 0 24 65 1 0 25 66 1 0 26 67 1 0 26 68 1 0 26 69 1 0 27 70 1 0 28 71 1 0 29 72 1 0 31 73 1 0 31 74 1 0 31 75 1 0 34 76 1 0 M END

Standard InCHIKey	HQKNXSLBDXDYEF-ZMTCAJFBSA-N
Standard InCHI	InChI=1S/C30H42O4/c1-19(11-9-13-21(3)27(33)34)10-8-12-20(2)26-22(31)18-24-29(6)17-15-25(32)28(4,5)23(29)14-16-30(24,26)7/h8-13,23-25,32H,14-18H2,1-7H3,(H,33,34)/b11-9+,12-8+,19-10+,21-13+,26-20-/t23-,24-,25-,29-,30-/m0/s1
SMILES	C/C(=CC=CC(=C/1C(=O)C[C@H]2[C@@]3(C)CC[C@@H](C(C)(C)[C@@H]3CC[C@]12C)O)C)/C=C/C=C(C)/C(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	466.31	Volume:	518.472 ? Van der Waals volume.
Dense:	0.899	LogP:	3.5 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.848 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.517 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	22.0
TPSA:	74.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.354	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.69	Fsp³:	0.6
MCE-18:	66.375 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.687	Fluc inhibitor:	0.49 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.152 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.028 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.6	Promiscuous compounds:	0.335

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.167	MDCK Permeability:	-4.866
Pgp-inhibitor:	0.006	Pgp-substrate:	0.609
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):	0.013
20% Bioavailability (F20%):	0.592	30% Bioavailability (F30%):	0.394
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.969
Plasma Protein Binding (PPB):	97.393%	Volume Distribution (VD):	-0.566
Fu:	3.008% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.002
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.04	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.614	CYP2C19-substrate:	0.049
CYP2C9-inhibitor:	0.566	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.337	CYP3A4-substrate:	0.032
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.877
HLM stability:	0.021 ? 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):

2.852

Half-life (T1/2):

1.054

ADMET: Toxicity

hERG Blockers:	0.031	hERG Blockers (10um):	0.062
Human Hepatotoxicity (H-HT):	0.623	Drug-induced Liver Injury (DILI):	0.767
AMES Toxicity:	0.523	Rat Oral Acute Toxicity:	0.601
Maximum Recommended Daily Dose:	0.644	Skin Sensitization:	0.966
Carcinogencity:	0.741	Eye Corrosion:	0.011
Eye Irritation:	0.53	Respiratory Toxicity:	0.872
Drug-induced Neurotoxicity:	0.122	Ototoxicity:	0.687
Hematotoxicity:	0.621	Drug-induced Nephrotoxicity:	0.913
Genotoxicity:	0.889	RPMI-8226 Immunitoxicity:	0.061
A549 Cytotoxicity:	0.092	Hek293 Cytotoxicity:	0.149
BCF:	0.955 ? 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:	4.039 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.463 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.828 ? 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
NPO33155	stelletta tenuis	Species	Ancorinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17604394]
NPO33155	stelletta tenuis	Species	Ancorinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7807129]

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	4

Activity Type	# Activity
Cell line	4

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
NPT81	Cell line	A549	Homo sapiens	IC50	=	28000.0	nM	PMID[9784156]
NPT659	Cell line	SMMC-7721	Homo sapiens	IC50	=	120000.0	nM	PMID[9784156]
NPT196	Cell line	AGS	Homo sapiens	IC50	=	3900.0	nM	PMID[18276144]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	33000.0	nM	PMID[18725180]

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 NPC250757 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	18603
0.1-0.2	26547
0.2-0.3	4178
0.3-0.4	460
0.4-0.5	44
0.5-0.6	11
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
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	NPC301534
0.7121	Intermediate Similarity	NPC3856
0.7121	Intermediate Similarity	NPC57079
0.7121	Intermediate Similarity	NPC108368
0.7121	Intermediate Similarity	NPC279639
0.6857	Remote Similarity	NPC474018
0.6857	Remote Similarity	NPC473986
0.6515	Remote Similarity	NPC310752
0.6377	Remote Similarity	NPC471153
0.6324	Remote Similarity	NPC141292
0.6286	Remote Similarity	NPC88310
0.6143	Remote Similarity	NPC474785
0.5946	Remote Similarity	NPC475050
0.5775	Remote Similarity	NPC299100
0.5714	Remote Similarity	NPC330011
0.557	Remote Similarity	NPC475065
0.5309	Remote Similarity	NPC475163
0.527	Remote Similarity	NPC474690
0.527	Remote Similarity	NPC292491
0.5128	Remote Similarity	NPC32577
0.5067	Remote Similarity	NPC473435
0.5067	Remote Similarity	NPC473280
0.5067	Remote Similarity	NPC471078

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC250757 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5871
0.1-0.2	3170
0.2-0.3	107
0.3-0.4	2
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