NPASS Compound

Natural Product: NPC476355

Natural Product ID	NPC476355
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Crassumolide C
IUPAC Name	methyl (3aS,6E,10Z,14E,15aS)-6,14-dimethyl-3-methylidene-2-oxo-3a,4,5,8,9,12,13,15a-octahydrocyclotetradeca[b]furan-10-carboxylate
Synonyms	Crassumolide C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL577376
PubChem CID	25156698
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones [CHEMONTID:0002502] Cembranolides

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 53 54 0 0 0 0 0 0 0 0999 V2000 -1.1998 3.4376 -2.1898 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6801 2.4503 -1.1286 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6031 2.3989 -1.0452 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4475 1.5981 -0.1708 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1477 0.5369 -1.0290 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8030 -0.4662 -0.2002 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5814 -1.7299 -0.2781 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6956 -2.4974 -1.1412 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7778 -3.4107 -0.3988 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5427 -2.9162 -0.0031 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0874 -1.7640 -0.3093 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4211 -1.3709 0.1486 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4002 -0.1847 1.0876 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2429 0.7496 0.6576 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7024 1.6914 -0.3832 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6533 0.5012 0.8285 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2199 1.5014 1.4999 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2270 -0.1275 -0.3555 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4131 0.0795 -0.7675 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2576 -0.9517 -0.9037 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4032 -3.7787 0.8409 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8088 -0.0124 0.7855 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4252 -0.8411 1.5399 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1038 1.3206 0.9083 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0637 1.7941 1.8401 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1033 2.9540 -3.1796 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5913 4.3431 -2.1860 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2730 3.6450 -2.0264 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1698 3.0644 -1.7538 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3483 2.3417 0.1109 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1717 1.2911 0.7993 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3539 0.1463 -1.6937 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8609 1.0602 -1.7065 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1620 -2.3658 0.4352 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3819 -3.0871 -1.8323 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1336 -1.8488 -1.8709 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3383 -3.8411 0.4991 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6848 -4.3368 -1.0650 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5043 -1.1841 -0.9352 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9683 -2.1757 0.6807 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2472 -0.4932 2.1392 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4309 0.1252 0.2786 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9221 1.2503 1.6011 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4997 2.4054 0.0221 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2949 1.1447 -1.1906 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1539 1.9392 1.2227 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7064 1.8911 2.3725 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5930 -3.1906 1.7835 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3386 -4.0883 0.3455 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8662 -4.6871 1.1518 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9379 1.1159 1.7778 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6121 1.7514 2.8499 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3309 2.8214 1.5373 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 3 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 3 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 13 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 18 20 1 0 10 21 1 0 6 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 15 2 1 0 20 12 1 0 1 26 1 0 1 27 1 0 1 28 1 0 3 29 1 0 4 30 1 0 4 31 1 0 5 32 1 0 5 33 1 0 7 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 11 39 1 0 12 40 1 0 13 41 1 0 14 42 1 0 14 43 1 0 15 44 1 0 15 45 1 0 17 46 1 0 17 47 1 0 21 48 1 0 21 49 1 0 21 50 1 0 25 51 1 0 25 52 1 0 25 53 1 0 M END

Standard InCHIKey	APOQWKMQOYCBGK-RPRNLCBVSA-N
Standard InCHI	InChI=1S/C21H28O4/c1-14-7-5-9-17(21(23)24-4)10-6-8-15(2)13-19-18(12-11-14)16(3)20(22)25-19/h7,10,13,18-19H,3,5-6,8-9,11-12H2,1-2,4H3/b14-7+,15-13+,17-10-/t18-,19-/m0/s1
SMILES	CC1=CCCC(=CCCC(=CC2C(CC1)C(=C)C(=O)O2)C)C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	344.2	Volume:	374.001 ? Van der Waals volume.
Dense:	0.92	LogP:	3.087 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.089 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.844 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	21.0
TPSA:	52.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.401	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.343	Fsp³:	0.524
MCE-18:	35.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.344	Fluc inhibitor:	0.023 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.019 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.518 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.716	Promiscuous compounds:	0.004

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.609	MDCK Permeability:	-4.679
Pgp-inhibitor:	0.887	Pgp-substrate:	0.008
PAMPA:	0.131 ? 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):	0.046
20% Bioavailability (F20%):	0.072	30% Bioavailability (F30%):	0.664
50% Bioavailability (F50%):	0.876

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.21	MRP1:	0.991
Plasma Protein Binding (PPB):	97.628%	Volume Distribution (VD):	0.097
Fu:	2.435% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.026
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.455	CYP1A2-substrate:	0.939
CYP2C19-inhibitor:	0.822	CYP2C19-substrate:	0.504
CYP2C9-inhibitor:	0.926	CYP2C9-substrate:	0.037
CYP2D6-inhibitor:	0.838	CYP2D6-substrate:	0.953
CYP3A4-inhibitor:	0.034	CYP3A4-substrate:	0.378
CYP2B6-substrate:	0.145	CYP2C8-inhibitor:	0.949
HLM stability:	0.997 ? 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):

7.801

Half-life (T1/2):

1.264

ADMET: Toxicity

hERG Blockers:	0.009	hERG Blockers (10um):	0.248
Human Hepatotoxicity (H-HT):	0.643	Drug-induced Liver Injury (DILI):	0.853
AMES Toxicity:	0.101	Rat Oral Acute Toxicity:	0.083
Maximum Recommended Daily Dose:	0.61	Skin Sensitization:	0.987
Carcinogencity:	0.723	Eye Corrosion:	0.371
Eye Irritation:	0.91	Respiratory Toxicity:	0.065
Drug-induced Neurotoxicity:	0.67	Ototoxicity:	0.501
Hematotoxicity:	0.351	Drug-induced Nephrotoxicity:	0.409
Genotoxicity:	0.067	RPMI-8226 Immunitoxicity:	0.084
A549 Cytotoxicity:	0.155	Hek293 Cytotoxicity:	0.118
BCF:	1.435 ? 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:	4.181 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.861 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.293 ? 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
NPO27251	Lobophytum crassum	Species	Alcyoniidae	Eukaryota	n.a.	south china sea	n.a.	PMID[18512986]
NPO27251	Lobophytum crassum	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18973388]
NPO27251	Lobophytum crassum	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9548852]
NPO27251	Lobophytum crassum	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27251	Lobophytum crassum	Species	Alcyoniidae	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	6
Activity	2

Activity Type	# Activity
Cell line	7
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
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	5.0	ug.mL-1	DOI[10.6019/CHEMBL1201861]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	>	5.0	ug.mL-1	DOI[10.6019/CHEMBL1201861]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	5.0	ug.mL-1	PMID[8277308]
NPT81	Cell line	A549	Homo sapiens	IC50	>	5.0	ug.mL-1	PMID[8277308]
NPT1031	Cell line	Ca9-22	Homo sapiens	IC50	=	1.7	ug.mL-1	PMID[22608855]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	2.3	%	PMID[2832544]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	34.5	%	PMID[11076561]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	5.0	ug.mL-1	PMID[18973388]

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 NPC476355 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	20500
0.1-0.2	25950
0.2-0.3	2976
0.3-0.4	351
0.4-0.5	53
0.5-0.6	18
0.6-0.7	4
0.7-0.8	0
0.8-0.85	4
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	NPC58956
0.8333	Intermediate Similarity	NPC163003
0.8333	Intermediate Similarity	NPC295633
0.8333	Intermediate Similarity	NPC269206
0.7	Intermediate Similarity	NPC7563
0.6863	Remote Similarity	NPC123360
0.6383	Remote Similarity	NPC601805
0.6071	Remote Similarity	NPC93763
0.6	Remote Similarity	NPC140287
0.5965	Remote Similarity	NPC108816
0.5849	Remote Similarity	NPC470256
0.5714	Remote Similarity	NPC267231
0.5714	Remote Similarity	NPC250315
0.5636	Remote Similarity	NPC194871
0.56	Remote Similarity	NPC235906
0.5577	Remote Similarity	NPC196653
0.5577	Remote Similarity	NPC603669
0.5472	Remote Similarity	NPC471465
0.5385	Remote Similarity	NPC171204
0.5385	Remote Similarity	NPC606745
0.5345	Remote Similarity	NPC20713
0.5283	Remote Similarity	NPC611318
0.5192	Remote Similarity	NPC167881
0.5192	Remote Similarity	NPC98557
0.5098	Remote Similarity	NPC129665
0.5094	Remote Similarity	NPC329852
0.5091	Remote Similarity	NPC480697

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476355 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7030
0.1-0.2	2084
0.2-0.3	30
0.3-0.4	5
0.4-0.5	1
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