NPASS Compound

Natural Product: NPC16569

Natural Product ID	NPC16569
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NXCIXUFRIWJEEC-KQERWQABSA-N
IUPAC Name	n.a.
Synonyms	6'-Hydroxycalactin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL559102
PubChem CID	44179786
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides and derivatives

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 79 85 0 0 0 0 0 0 0 0999 V2000 -4.4661 1.7986 -0.0542 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0429 0.4583 0.4689 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9868 0.7752 1.5248 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6697 1.1842 0.8664 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1698 -0.0794 0.2306 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0921 -0.5712 -0.8159 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6498 -2.0171 -1.1421 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2320 -1.9039 -1.7491 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7080 -1.3280 -0.7232 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0937 -1.3257 -1.3127 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0671 -0.5308 -0.4870 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5316 0.7170 0.1153 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1937 0.5128 0.7551 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2318 0.0213 -0.3208 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3559 0.9804 -1.4440 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5357 1.7557 -1.7434 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4628 1.1787 1.0496 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7486 1.1669 0.6248 C 0 0 1 0 0 0 0 0 0 0 0 0 5.5850 0.4921 1.7239 C 0 0 1 0 0 0 0 0 0 0 0 0 7.0748 0.6661 1.4025 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2735 0.4937 -0.0793 C 0 0 1 0 0 0 0 0 0 0 0 0 8.5240 -0.3229 -0.3798 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6556 -0.5579 -1.7399 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1974 -0.2745 -0.5548 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0785 0.5849 -0.6789 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1110 -0.1491 -1.3285 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3268 1.1692 2.8969 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1986 2.5116 0.6300 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5577 -0.5201 -0.5470 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1696 -1.8262 -0.1135 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7283 -1.6598 1.2789 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1715 -0.1835 1.2136 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.5178 -0.0842 0.6756 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0426 0.4389 -0.4007 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5081 0.2456 -0.4422 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2955 0.6288 -1.3377 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.8371 -0.4319 0.6853 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6989 -0.6738 1.4218 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1738 -0.1815 -1.7570 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4549 1.8881 -1.1597 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7357 2.6240 0.2603 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4238 2.1763 0.3834 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7849 -0.1510 2.0904 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3972 1.5613 2.1782 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0188 1.4747 1.7335 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8096 2.0099 0.1694 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0988 -0.8492 1.0529 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8387 -0.0476 -1.7639 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5096 -2.6243 -0.2532 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2561 -2.4546 -1.9548 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0915 -2.9550 -1.9425 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2480 -1.3565 -2.6928 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6613 -1.9852 0.1753 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0610 -0.9848 -2.3692 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4476 -2.3780 -1.3303 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5004 -1.2181 0.2956 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5152 1.5152 -0.6728 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2890 -0.2739 1.5093 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8975 1.4947 1.1809 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2462 1.0475 -2.0669 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3170 -0.5630 1.8375 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5986 -0.1657 1.9182 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4329 1.6607 1.7643 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2503 1.4341 -0.6265 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4715 -1.3111 0.1148 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4400 0.1747 0.0141 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8449 0.3012 -2.1835 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4258 1.3640 -1.4216 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8405 2.0193 2.9870 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0380 2.9029 -0.2840 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5168 -2.6889 -0.1115 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0568 -2.1178 -0.7500 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9127 -1.8034 2.0051 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5805 -2.3372 1.4349 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2029 0.1252 2.2952 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5642 0.9485 -1.2069 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7279 -0.2636 2.4539 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5212 -1.7644 1.4847 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5829 0.4125 -2.3176 H 0 0 0 0 0 0 0 0 0 0 0 0 2 1 1 6 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 6 15 16 2 0 12 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 21 24 1 0 24 25 1 0 25 26 1 0 19 27 1 0 18 28 1 6 6 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 35 37 1 0 37 38 1 0 29 39 1 6 32 2 1 0 38 33 1 0 29 2 1 0 14 5 1 0 25 18 1 0 14 9 1 0 26 11 1 0 1 40 1 0 1 41 1 0 1 42 1 0 3 43 1 0 3 44 1 0 4 45 1 0 4 46 1 0 5 47 1 1 6 48 1 6 7 49 1 0 7 50 1 0 8 51 1 0 8 52 1 0 9 53 1 1 10 54 1 0 10 55 1 0 11 56 1 1 12 57 1 6 13 58 1 0 13 59 1 0 15 60 1 0 19 61 1 1 20 62 1 0 20 63 1 0 21 64 1 6 22 65 1 0 22 66 1 0 23 67 1 0 25 68 1 6 27 69 1 0 28 70 1 0 30 71 1 0 30 72 1 0 31 73 1 0 31 74 1 0 32 75 1 1 34 76 1 0 38 77 1 0 38 78 1 0 39 79 1 0 M END

Standard InCHIKey	NXCIXUFRIWJEEC-KQERWQABSA-N
Standard InCHI	InChI=1S/C29H40O10/c1-26-6-4-19-20(28(26,34)7-5-18(26)15-8-24(33)36-13-15)3-2-16-9-21-22(11-27(16,19)14-31)39-29(35)23(32)10-17(12-30)37-25(29)38-21/h8,14,16-23,25,30,32,34-35H,2-7,9-13H2,1H3/t16-,17-,18+,19-,20+,21+,22+,23+,25-,26+,27+,28-,29-/m0/s1
SMILES	C[C@@]12CC[C@H]3[C@@H](CC[C@H]4C[C@@H]5[C@@H](C[C@]34C=O)O[C@]3([C@@H](C[C@@H](CO)O[C@H]3O5)O)O)[C@]2(CC[C@@H]1C1=CC(=O)OC1)O

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	roots	Wadi Um Hebal, Egypt	2001-JAN	PMID[16989527]
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19555122]
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	Aerial Parts	n.a.	n.a.	PMID[30629433]
NPO33139	Pergularia tomentosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	5
Non-molecular	1
Others	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
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	300.0	nM	PMID[17035027]
NPT1081	Cell line	BXPC-3	Homo sapiens	IC50	=	600.0	nM	PMID[17035027]
NPT114	Cell line	LoVo	Homo sapiens	IC50	=	900.0	nM	PMID[16480866]
NPT81	Cell line	A549	Homo sapiens	IC50	=	80.0	nM	PMID[16480866]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	500.0	nM	PMID[16480866]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	400.0	nM	PMID[19555122]
NPT2	Others	Unspecified	n.a.	IC50	=	500.0	nM	PMID[16480866]

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 NPC16569 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	15013
0.1-0.2	32386
0.2-0.3	2218
0.3-0.4	77
0.4-0.5	111
0.5-0.6	24
0.6-0.7	13
0.7-0.8	0
0.8-0.85	2
0.85-0.9	3
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC488161
0.8831	High Similarity	NPC253456
0.8831	High Similarity	NPC159338
0.85	High Similarity	NPC329905
0.8072	Intermediate Similarity	NPC488158
0.8072	Intermediate Similarity	NPC488159
0.7882	Intermediate Similarity	NPC225385
0.7805	Intermediate Similarity	NPC277374
0.7349	Intermediate Similarity	NPC104585
0.7262	Intermediate Similarity	NPC171619
0.7209	Intermediate Similarity	NPC488162
0.7209	Intermediate Similarity	NPC93416
0.7093	Intermediate Similarity	NPC42670
0.7093	Intermediate Similarity	NPC19124
0.7045	Intermediate Similarity	NPC475136
0.6932	Remote Similarity	NPC157817
0.6818	Remote Similarity	NPC91
0.6667	Remote Similarity	NPC163365
0.6632	Remote Similarity	NPC476221
0.6632	Remote Similarity	NPC477709
0.6559	Remote Similarity	NPC480905
0.6559	Remote Similarity	NPC470094
0.6444	Remote Similarity	NPC609258
0.6404	Remote Similarity	NPC488160
0.6383	Remote Similarity	NPC85369
0.6374	Remote Similarity	NPC474466
0.6316	Remote Similarity	NPC473040
0.6	Remote Similarity	NPC488163
0.5914	Remote Similarity	NPC79193
0.5745	Remote Similarity	NPC298783
0.5652	Remote Similarity	NPC480914
0.5625	Remote Similarity	NPC33934
0.561	Remote Similarity	NPC196931
0.5567	Remote Similarity	NPC142756
0.5376	Remote Similarity	NPC469750
0.5376	Remote Similarity	NPC480915
0.5357	Remote Similarity	NPC222875
0.5357	Remote Similarity	NPC25177
0.5354	Remote Similarity	NPC188234
0.5301	Remote Similarity	NPC268829
0.5301	Remote Similarity	NPC295110
0.5263	Remote Similarity	NPC88668
0.5263	Remote Similarity	NPC250556
0.5146	Remote Similarity	NPC329986
0.5146	Remote Similarity	NPC140092
0.5098	Remote Similarity	NPC125077
0.5059	Remote Similarity	NPC480913
0.5053	Remote Similarity	NPC5311
0.5053	Remote Similarity	NPC77299
0.5053	Remote Similarity	NPC480906
0.5049	Remote Similarity	NPC232785
0.5049	Remote Similarity	NPC486139

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC16569 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6223
0.1-0.2	2855
0.2-0.3	58
0.3-0.4	8
0.4-0.5	4
0.5-0.6	2
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
0.55	Remote Similarity	NPD7625	Phase 1
0.5263	Remote Similarity	NPD7507	Pre-clinical

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