NPASS Compound

Natural Product: NPC322878

Natural Product ID	NPC322878
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Phakellistatin 14
IUPAC Name	methyl 2-[(3S,6S,9S,12S,15S,18S,21S)-18-benzyl-3-[(2S)-butan-2-yl]-6,12-dimethyl-9-(2-methylsulfinylethyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazabicyclo[19.3.0]tetracosan-15-yl]acetate
Synonyms	phakellistatin 14
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL502751
PubChem CID	11308763
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000348] Peptides [CHEMONTID:0004831] Oligopeptides

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 107109 0 0 0 0 0 0 0 0999 V2000 -2.1959 -5.8151 3.1987 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3952 -4.6974 2.3685 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5180 -4.6364 1.5595 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3219 -5.5952 1.6028 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8129 -3.5110 0.6582 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7659 -2.4331 0.7107 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0407 -1.3296 -0.1618 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.0485 -0.5444 -0.0687 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9386 -0.8036 0.9753 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2222 0.5575 -1.0234 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9182 0.0617 -2.4341 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8157 -1.0034 -2.8993 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0431 -0.6349 -3.4776 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9255 -1.5777 -3.9558 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6124 -2.9184 -3.8724 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4132 -3.2886 -3.3083 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5339 -2.3103 -2.8303 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6393 1.7775 -0.7193 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.8223 2.2030 0.1448 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3222 1.3140 1.0629 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4728 3.5998 0.1135 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7872 4.2431 -1.2594 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0905 5.5753 -1.2045 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3943 5.5071 0.1859 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1536 4.1020 0.3036 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0531 3.4176 0.4645 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1491 2.1588 0.2202 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4078 3.8127 0.8150 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3727 3.0844 0.0876 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1070 2.1165 0.2719 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2740 1.2387 1.4794 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3163 -0.1256 1.1633 N 0 0 0 0 0 0 0 0 0 0 0 0 3.7823 -1.1725 1.6027 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5353 -2.4676 0.8492 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6549 -2.2868 -0.2379 N 0 0 0 0 0 0 0 0 0 0 0 0 1.5063 -2.7548 -0.3839 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8127 -3.6269 0.5955 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4562 -3.0995 0.9231 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.4742 -3.0431 0.1810 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4295 -3.5298 -1.1131 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8390 -5.0750 0.1657 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8479 -2.4118 -1.5805 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8735 -2.9485 0.2346 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3865 -1.8862 -0.7080 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9435 -2.4221 -1.4359 S 0 0 0 0 0 0 0 0 0 0 0 0 7.4456 -1.3845 -2.4182 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6862 -3.9615 -2.3531 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5351 -1.2996 2.7523 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4559 1.6575 2.2973 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9523 1.7342 -0.8009 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7627 5.2361 0.9520 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2791 5.3462 1.2847 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5797 6.8514 1.3977 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1241 5.8235 2.2288 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7706 -5.7266 4.1481 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5361 -6.7336 2.6911 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1284 -5.9617 3.4804 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8648 -3.9498 -0.3818 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8303 -3.1122 0.8367 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5965 -2.1066 1.7428 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5927 -0.9744 1.9281 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3721 0.7337 -1.0840 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8368 -0.2193 -2.5284 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0173 0.9617 -3.1093 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2796 0.4348 -3.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8777 -1.2763 -4.4053 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2918 -3.6733 -4.2416 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1810 -4.3327 -3.2480 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6214 -2.6762 -2.4200 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8792 0.7527 1.6830 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1276 4.1976 0.8539 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3403 3.6101 -2.0615 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8664 4.3851 -1.3842 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2421 5.6442 -1.9305 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7584 6.4418 -1.2418 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5788 6.1970 0.2054 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2319 5.7738 0.8841 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5295 3.4086 1.9240 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3334 1.4060 2.1010 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2726 -3.1977 1.6079 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4088 -3.5675 1.5677 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0287 -4.3925 -1.4046 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6252 -5.6148 0.7522 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1006 -5.1981 -0.9051 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1145 -5.5713 0.4155 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4044 -2.1344 -2.3777 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6214 -3.1678 1.0029 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6414 -3.8423 -0.3418 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5538 -0.9566 -0.1428 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6212 -1.6709 -1.4874 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8572 -4.5079 -1.8546 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6032 -4.5613 -2.3241 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3834 -3.6743 -3.3875 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3103 -0.7399 2.9979 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4135 2.7819 2.3806 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4202 1.3314 1.9160 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3551 1.3224 3.3605 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7951 2.1221 -1.7222 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6660 5.8821 0.0802 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4690 4.8744 2.2589 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8138 4.9762 0.4279 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6391 7.0089 1.1158 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3378 7.2174 2.4121 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9529 7.3296 0.6153 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9002 5.8460 3.0093 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8671 6.8709 1.9928 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2486 5.2063 2.5256 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 3 5 1 0 5 6 1 0 6 7 1 0 7 8 2 3 8 9 1 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 10 18 1 0 18 19 2 3 19 20 1 0 19 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 0 29 30 2 3 30 31 1 0 31 32 1 0 32 33 2 3 33 34 1 0 34 35 1 0 35 36 2 3 36 37 1 0 37 38 1 0 38 39 2 3 39 40 1 0 37 41 1 0 36 42 1 0 34 43 1 0 43 44 1 0 44 45 1 0 45 46 2 0 45 47 1 0 33 48 1 0 31 49 1 0 30 50 1 0 28 51 1 0 51 52 1 0 52 53 1 0 51 54 1 0 39 6 1 0 17 12 1 0 25 21 1 0 1 55 1 0 1 56 1 0 1 57 1 0 5 58 1 0 5 59 1 0 6 60 1 1 9 61 1 0 10 62 1 6 11 63 1 0 11 64 1 0 13 65 1 0 14 66 1 0 15 67 1 0 16 68 1 0 17 69 1 0 20 70 1 0 21 71 1 1 22 72 1 0 22 73 1 0 23 74 1 0 23 75 1 0 24 76 1 0 24 77 1 0 28 78 1 1 31 79 1 1 34 80 1 1 37 81 1 1 40 82 1 0 41 83 1 0 41 84 1 0 41 85 1 0 42 86 1 0 43 87 1 0 43 88 1 0 44 89 1 0 44 90 1 0 47 91 1 0 47 92 1 0 47 93 1 0 48 94 1 0 49 95 1 0 49 96 1 0 49 97 1 0 50 98 1 0 51 99 1 6 52100 1 0 52101 1 0 53102 1 0 53103 1 0 53104 1 0 54105 1 0 54106 1 0 54107 1 0 M END

Standard InCHIKey	ZBIJFJOAXJXGTR-KLZQDHKKSA-N
Standard InCHI	InChI=1S/C36H53N7O10S/c1-7-20(2)29-36(51)43-16-11-14-27(43)35(50)41-25(18-23-12-9-8-10-13-23)34(49)40-26(19-28(44)53-5)33(48)38-21(3)30(45)39-24(15-17-54(6)52)32(47)37-22(4)31(46)42-29/h8-10,12-13,20-22,24-27,29H,7,11,14-19H2,1-6H3,(H,37,47)(H,38,48)(H,39,45)(H,40,49)(H,41,50)(H,42,46)/t20-,21-,22-,24-,25-,26-,27-,29-,54?/m0/s1
SMILES	COC(=O)C[C@@H]1N=C(O)[C@H](Cc2ccccc2)N=C(O)[C@@H]2CCCN2C(=O)[C@@H](N=C([C@@H](N=C([C@@H](N=C([C@@H](N=C1O)C)O)CCS(=O)C)O)C)O)[C@H](CC)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	775.36	Volume:	759.93 ? Van der Waals volume.
Dense:	1.02	LogP:	-0.804 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.786 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.846 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	33.0
TPSA:	265.21 ? Topological Polar Surface Area.	H-Bond Acceptor:	17.0
H-Bond Donor:	6.0	Rings:	3.0
Heavy Atoms:	18.0

MedChem Properties

QED Drug-Likeness Score:	0.157	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.476	Fsp³:	0.611
MCE-18:	93.655 ? 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:	0.336	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.04 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.401 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.187	Promiscuous compounds:	0.003

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.414	MDCK Permeability:	-4.979
Pgp-inhibitor:	0.853	Pgp-substrate:	1.0
PAMPA:	0.836 ? 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):	0.945
20% Bioavailability (F20%):	1.0	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.975
Plasma Protein Binding (PPB):	62.553%	Volume Distribution (VD):	-0.177
Fu:	35.501% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.979
OATP1B3 inhibitor:	0.668	BCRP inhibitor:	0.098
BSEP inhibitor:	0.913

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.413	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.25 ? 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):

0.862

Half-life (T1/2):

2.513

ADMET: Toxicity

hERG Blockers:	0.0	hERG Blockers (10um):	0.0
Human Hepatotoxicity (H-HT):	1.0	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.067	Rat Oral Acute Toxicity:	0.97
Maximum Recommended Daily Dose:	0.382	Skin Sensitization:	1.0
Carcinogencity:	0.463	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.775
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.998
Hematotoxicity:	0.797	Drug-induced Nephrotoxicity:	1.0
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.0
A549 Cytotoxicity:	0.0	Hek293 Cytotoxicity:	0.0
BCF:	0.293 ? 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:	3.096 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.733 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.738 ? 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
NPO30912	Phakellia	Genus	Bubaridae	Eukaryota	n.a.	n.a.	n.a.	PMID[15679318]

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
ED50	1

Activity Type	# Activity
Cell line	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
NPT168	Cell line	P388	Mus musculus	ED50	=	5.0	ug ml-1	PMID[15679318]

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 NPC322878 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	15153
0.1-0.2	32885
0.2-0.3	1389
0.3-0.4	329
0.4-0.5	72
0.5-0.6	27
0.6-0.7	2
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8077	Intermediate Similarity	NPC489822
0.6667	Remote Similarity	NPC479070
0.6092	Remote Similarity	NPC479072
0.5802	Remote Similarity	NPC200589
0.5747	Remote Similarity	NPC479068
0.5745	Remote Similarity	NPC479069
0.5686	Remote Similarity	NPC489823
0.5638	Remote Similarity	NPC241794
0.5632	Remote Similarity	NPC489591
0.5579	Remote Similarity	NPC489827
0.5568	Remote Similarity	NPC248283
0.5444	Remote Similarity	NPC489824
0.5393	Remote Similarity	NPC287401
0.5326	Remote Similarity	NPC489556
0.5319	Remote Similarity	NPC479074
0.53	Remote Similarity	NPC489828
0.5222	Remote Similarity	NPC202198
0.5222	Remote Similarity	NPC489557
0.5217	Remote Similarity	NPC489592
0.5213	Remote Similarity	NPC5194
0.5161	Remote Similarity	NPC6975
0.5143	Remote Similarity	NPC110602
0.5143	Remote Similarity	NPC479071
0.5114	Remote Similarity	NPC242482
0.5111	Remote Similarity	NPC255447
0.5056	Remote Similarity	NPC489593
0.5056	Remote Similarity	NPC224315
0.5055	Remote Similarity	NPC200964
0.5052	Remote Similarity	NPC489825
0.5045	Remote Similarity	NPC75726

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC322878 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2972
0.1-0.2	5723
0.2-0.3	420
0.3-0.4	32
0.4-0.5	3
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