NPASS Compound

Natural Product: NPC275837

Natural Product ID	NPC275837
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Sumalarin B
IUPAC Name	2-acetyloxyethyl (2S)-2-acetyloxy-3-[[(5S,9S)-13,15-dihydroxy-5-methyl-3,11-dioxo-4-oxabicyclo[10.4.0]hexadeca-1(12),13,15-trien-9-yl]sulfanyl]propanoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3087768
PubChem CID	72945490
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000147] Macrolides and analogues

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 69 70 0 0 0 0 0 0 0 0999 V2000 2.6069 5.0522 -0.4308 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8189 3.7753 -1.1236 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9682 3.7147 -2.3517 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8549 2.5888 -0.3855 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0521 1.3377 -0.9756 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2861 0.6876 -0.4583 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9884 1.2989 0.4104 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7053 -0.5410 -0.8717 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8396 -1.2359 -0.4562 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0744 -0.4655 -0.7884 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2701 -1.1120 -0.3984 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5881 -1.4494 0.8852 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8038 -1.1904 1.8127 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8648 -2.1354 1.2594 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9014 0.3718 -0.7500 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3614 0.9979 -1.4251 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.9647 -0.1437 -1.1807 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4713 -0.3479 0.1888 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7006 -0.8192 1.3390 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6654 -1.2102 2.4749 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6724 -0.1837 2.8355 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5729 -0.7343 3.9780 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5701 -0.0078 1.7300 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0366 1.1656 1.2474 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6765 2.2352 1.8627 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8954 1.3449 0.0924 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3666 0.1822 -0.6582 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6507 -0.6578 -1.4752 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2327 -0.6778 -1.7390 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7318 -1.8858 -1.7327 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2478 0.3501 -2.0075 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3954 -1.6741 -2.1264 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6302 -2.5222 -2.9634 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7389 -1.8592 -1.9896 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4436 -1.0256 -1.1772 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7557 -0.0356 -0.5360 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8377 -1.1683 -0.9949 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4432 5.2135 0.2699 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6060 5.8705 -1.1852 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6335 5.0540 0.1282 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1655 1.5031 -2.0691 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8287 -1.4805 0.6276 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8768 -2.2084 -1.0147 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1407 -0.4097 -1.9160 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0042 0.5546 -0.4041 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6613 -3.0060 1.8820 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4764 -1.3763 1.7927 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4402 -2.4311 0.3459 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1633 -0.5613 -1.3065 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8277 0.0895 0.2973 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7385 -1.1144 -1.6585 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4716 -0.8281 0.0986 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7471 0.7617 0.5013 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1331 -1.7293 1.0964 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0213 -0.0656 1.7394 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1223 -2.1829 2.2168 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0101 -1.4030 3.3557 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3053 0.7630 3.2505 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8666 -1.1497 4.7189 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1840 -1.5404 3.5365 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1796 0.0979 4.3833 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3559 2.0807 -0.5832 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7538 2.0077 0.4586 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8744 0.2493 -3.0494 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4532 1.3689 -1.7356 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0605 -2.0354 -3.6702 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2141 -2.6652 -2.5298 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3367 0.6317 0.1218 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2099 -2.0792 -1.2288 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 5 15 1 0 15 16 1 0 16 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 0 24 25 2 0 24 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 29 31 1 0 28 32 1 0 32 33 1 0 32 34 2 0 34 35 1 0 35 36 2 0 35 37 1 0 31 17 1 0 36 27 1 0 1 38 1 0 1 39 1 0 1 40 1 0 5 41 1 6 9 42 1 0 9 43 1 0 10 44 1 0 10 45 1 0 14 46 1 0 14 47 1 0 14 48 1 0 15 49 1 0 15 50 1 0 17 51 1 6 18 52 1 0 18 53 1 0 19 54 1 0 19 55 1 0 20 56 1 0 20 57 1 0 21 58 1 1 22 59 1 0 22 60 1 0 22 61 1 0 26 62 1 0 26 63 1 0 31 64 1 0 31 65 1 0 33 66 1 0 34 67 1 0 36 68 1 0 37 69 1 0 M END

Standard InCHIKey	QDQXSVXGAZHQLE-OSGPJOMKSA-N
Standard InCHI	InChI=1S/C25H32O11S/c1-14-5-4-6-19(37-13-22(36-16(3)27)25(32)34-8-7-33-15(2)26)12-21(30)24-17(10-23(31)35-14)9-18(28)11-20(24)29/h9,11,14,19,22,28-29H,4-8,10,12-13H2,1-3H3/t14-,19-,22+/m0/s1
SMILES	CC(=O)O[C@@H](C(=O)OCCOC(=O)C)CS[C@H]1CCC[C@H](C)OC(=O)Cc2c(C(=O)C1)c(O)cc(c2)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	540.17	Volume:	517.953 ? Van der Waals volume.
Dense:	1.043	LogP:	2.007 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.36 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.499 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	22.0
TPSA:	162.73 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.282	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.635	Fsp³:	0.56
MCE-18:	60.462 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.098	Fluc inhibitor:	0.295 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.038 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.305 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.161	Promiscuous compounds:	0.736

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.366	MDCK Permeability:	-4.809
Pgp-inhibitor:	0.214	Pgp-substrate:	0.118
PAMPA:	0.868 ? 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):	0.0
20% Bioavailability (F20%):	0.149	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.112
Plasma Protein Binding (PPB):	89.962%	Volume Distribution (VD):	-0.097
Fu:	9.506% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.001
BSEP inhibitor:	0.976

ADMET: Metabolism

CYP1A2-inhibitor:	0.632	CYP1A2-substrate:	0.084
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.016
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.13
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.997
CYP3A4-inhibitor:	0.007	CYP3A4-substrate:	0.098
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
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):

1.452

Half-life (T1/2):

1.234

ADMET: Toxicity

hERG Blockers:	0.011	hERG Blockers (10um):	0.147
Human Hepatotoxicity (H-HT):	0.387	Drug-induced Liver Injury (DILI):	0.995
AMES Toxicity:	0.979	Rat Oral Acute Toxicity:	0.1
Maximum Recommended Daily Dose:	0.259	Skin Sensitization:	1.0
Carcinogencity:	0.893	Eye Corrosion:	0.006
Eye Irritation:	0.537	Respiratory Toxicity:	0.012
Drug-induced Neurotoxicity:	0.293	Ototoxicity:	0.266
Hematotoxicity:	0.116	Drug-induced Nephrotoxicity:	0.992
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.126
A549 Cytotoxicity:	0.195	Hek293 Cytotoxicity:	0.303
BCF:	0.698 ? 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:	3.345 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.996 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.512 ? 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
NPO33114	penicillium sumatrense ma-92	Species	Aspergillaceae	Eukaryota	rhizosphere of the mangrove Lumnitzera racemosa	n.a.	n.a.	PMID[24195466]

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	7

Activity Type	# Activity
Cell line	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
NPT1312	Cell line	SW1990	Homo sapiens	IC50	=	11000.0	nM	PMID[12828457]
NPT90	Cell line	DU-145	Homo sapiens	IC50	=	7000.0	nM	PMID[24900349]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	8000.0	nM	PMID[22437114]
NPT1229	Cell line	Huh-7	Homo sapiens	IC50	=	5500.0	nM	PMID[18358571]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	4700.0	nM	PMID[24485782]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	4600.0	nM	PMID[21846091]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	6800.0	nM	PMID[24195466]

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 NPC275837 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	17449
0.1-0.2	31546
0.2-0.3	808
0.3-0.4	40
0.4-0.5	3
0.5-0.6	7
0.6-0.7	2
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
0.7031	Intermediate Similarity	NPC474849
0.7031	Intermediate Similarity	NPC65837
0.7031	Intermediate Similarity	NPC149372
0.6761	Remote Similarity	NPC55092
0.6486	Remote Similarity	NPC213224
0.5821	Remote Similarity	NPC178467
0.5821	Remote Similarity	NPC474771
0.5493	Remote Similarity	NPC475974
0.5352	Remote Similarity	NPC354984
0.5217	Remote Similarity	NPC605699
0.5211	Remote Similarity	NPC177307
0.5211	Remote Similarity	NPC9121

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC275837 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4770
0.1-0.2	4362
0.2-0.3	18
0.3-0.4	0
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