NPASS Compound

Natural Product: NPC49315

Natural Product ID	NPC49315
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cryptophycin 175
IUPAC Name	(3S,6R,10R,13E,16S)-10-[(3,5-dichloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[(E,2R)-4-phenylbut-3-en-2-yl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone
Synonyms	Cryptophycin 175
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL506269
PubChem CID	10604522
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0002010] Hybrid peptides

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 88 90 0 0 0 0 0 0 0 0999 V2000 7.2215 -4.8871 3.0199 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3584 -4.6282 1.9445 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8783 -3.3733 1.6714 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5865 -2.5077 0.8264 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0890 -3.0512 0.1232 Cl 0 0 0 0 0 0 0 0 0 0 0 0 6.0914 -1.2515 0.5576 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9009 -0.8093 1.1011 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2271 -1.6672 1.9228 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6939 -2.9341 2.2147 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8005 -4.0050 3.2699 Cl 0 0 0 0 0 0 0 0 0 0 0 0 4.4453 0.5459 0.7354 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6176 0.4154 -0.5280 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4908 -0.3599 -0.3720 N 0 0 0 0 0 0 0 0 0 0 0 0 2.1165 -1.5190 -0.4868 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9181 -2.5884 -0.8911 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6889 -1.8610 -0.1876 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1209 -0.8708 0.2007 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5632 -1.1315 0.5095 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3614 -0.2458 -0.4912 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0431 1.0608 -0.1703 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1681 1.9030 -0.8288 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5548 1.4883 -1.8471 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0004 3.2726 -0.2735 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1747 3.8429 -0.8881 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1544 4.3096 -0.0114 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9523 4.1918 1.2548 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4107 4.9326 -0.3996 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3089 4.1117 -1.2656 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6085 2.8489 -0.6309 N 0 0 0 0 0 0 0 0 0 0 0 0 3.3253 1.7422 -1.1533 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6962 1.7226 -2.3903 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0430 6.2176 -1.1547 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1219 4.1873 -0.7576 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4864 3.7545 -0.3709 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6282 3.6954 1.1281 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4543 4.8248 -0.8911 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8133 -0.6135 -0.4656 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0026 -2.0500 -0.8246 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6865 -2.8762 -0.0803 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8866 -4.2718 -0.4007 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6402 -5.0448 0.4759 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8703 -6.3788 0.2515 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3657 -7.0170 -0.8559 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6131 -6.2405 -1.7294 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3871 -4.8970 -1.4918 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4841 -0.2469 0.8249 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1480 -5.9840 3.2948 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9954 -4.3299 3.9401 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2540 -4.6583 2.6650 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6549 -0.6073 -0.0894 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3035 -1.3605 2.3602 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2810 1.2683 0.5998 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7437 0.9427 1.5286 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3093 -0.1003 -1.2887 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8971 -2.4336 -1.0477 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3890 -2.8623 -0.2972 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2936 0.1124 0.2966 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7963 -2.1879 0.3632 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7730 -0.7475 1.5057 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8878 -0.5585 -1.4677 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9108 3.3084 0.8047 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0020 5.2662 0.4793 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9446 3.9249 -2.2832 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3022 4.6764 -1.3145 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9320 2.2942 -2.6670 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5723 6.8785 -0.3876 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3517 6.0114 -1.9913 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0071 6.6727 -1.4996 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8830 5.2049 -0.3933 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9965 4.2366 -1.8701 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7705 2.7759 -0.8409 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6809 4.7340 1.5555 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5665 3.1701 1.4392 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7575 3.2097 1.6309 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1425 5.7794 -0.4419 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2387 4.9137 -1.9817 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4959 4.5355 -0.7134 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3035 -0.0232 -1.2656 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5451 -2.3859 -1.7419 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1199 -2.4258 0.8325 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0762 -4.6092 1.3828 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4618 -7.0106 0.9279 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5406 -8.0696 -1.0454 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2010 -6.7219 -2.6108 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7803 -4.3183 -2.2106 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5890 -0.2541 0.7666 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2259 0.8249 1.0626 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1846 -0.8322 1.6953 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 4 5 1 0 4 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 7 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 14 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 28 29 1 0 29 30 2 3 30 31 1 0 27 32 1 0 23 33 1 0 33 34 1 0 34 35 1 0 34 36 1 0 19 37 1 0 37 38 1 0 38 39 2 0 39 40 1 0 40 41 2 0 41 42 1 0 42 43 2 0 43 44 1 0 44 45 2 0 37 46 1 0 9 3 1 0 30 12 1 0 45 40 1 0 1 47 1 0 1 48 1 0 1 49 1 0 6 50 1 0 8 51 1 0 11 52 1 0 11 53 1 0 12 54 1 6 15 55 1 0 16 56 1 0 17 57 1 0 18 58 1 0 18 59 1 0 19 60 1 6 23 61 1 1 27 62 1 1 28 63 1 0 28 64 1 0 31 65 1 0 32 66 1 0 32 67 1 0 32 68 1 0 33 69 1 0 33 70 1 0 34 71 1 0 35 72 1 0 35 73 1 0 35 74 1 0 36 75 1 0 36 76 1 0 36 77 1 0 37 78 1 6 38 79 1 0 39 80 1 0 41 81 1 0 42 82 1 0 43 83 1 0 44 84 1 0 45 85 1 0 46 86 1 0 46 87 1 0 46 88 1 0 M END

Standard InCHIKey	WTWQLCDDGYJOLG-GAWFYVAGSA-N
Standard InCHI	InChI=1S/C35H42Cl2N2O7/c1-21(2)16-30-35(43)45-29(22(3)14-15-24-10-7-6-8-11-24)12-9-13-31(40)39-28(33(41)38-20-23(4)34(42)46-30)19-25-17-26(36)32(44-5)27(37)18-25/h6-11,13-15,17-18,21-23,28-30H,12,16,19-20H2,1-5H3,(H,38,41)(H,39,40)/b13-9+,15-14+/t22-,23-,28-,29+,30+/m1/s1
SMILES	COc1c(Cl)cc(cc1Cl)C[C@H]1N=C(O)/C=C/C[C@H](OC(=O)[C@@H](OC(=O)[C@@H](CN=C1O)C)CC(C)C)[C@@H](/C=C/c1ccccc1)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	672.24	Volume:	670.556 ? Van der Waals volume.
Dense:	1.003	LogP:	4.337 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.257 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.042 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	31.0
TPSA:	127.01 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.276	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.379	Fsp³:	0.429
MCE-18:	77.76 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.893 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.657 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.007	Promiscuous compounds:	0.186

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.108	MDCK Permeability:	-4.643
Pgp-inhibitor:	0.998	Pgp-substrate:	0.015
PAMPA:	0.001 ? 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%):	0.887	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.917
Plasma Protein Binding (PPB):	98.77%	Volume Distribution (VD):	-0.063
Fu:	1.096% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.476
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.127	CYP1A2-substrate:	0.713
CYP2C19-inhibitor:	0.782	CYP2C19-substrate:	0.866
CYP2C9-inhibitor:	0.149	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.732	CYP2D6-substrate:	0.821
CYP3A4-inhibitor:	0.375	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
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):

4.84

Half-life (T1/2):

1.099

ADMET: Toxicity

hERG Blockers:	0.057	hERG Blockers (10um):	0.009
Human Hepatotoxicity (H-HT):	1.0	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.316	Rat Oral Acute Toxicity:	0.331
Maximum Recommended Daily Dose:	0.996	Skin Sensitization:	1.0
Carcinogencity:	0.248	Eye Corrosion:	0.0
Eye Irritation:	0.127	Respiratory Toxicity:	0.979
Drug-induced Neurotoxicity:	0.992	Ototoxicity:	0.884
Hematotoxicity:	0.192	Drug-induced Nephrotoxicity:	1.0
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.048
A549 Cytotoxicity:	0.095	Hek293 Cytotoxicity:	0.282
BCF:	1.298 ? 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:	4.114 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.566 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.078 ? 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
NPO18618	Neurolaena lobata	Species	Asteraceae	Eukaryota	n.a.	aerial part	n.a.	DOI[10.1021/jo00416a020]
NPO3613	Eriobotrya deflexa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11473413]
NPO4541	Capnella lacertiliensis	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12608844]
NPO40970	Nostoc sp. GSV 224	Strain	Nostocaceae	Bacteria	n.a.	n.a.	n.a.	PMID[15332864]
NPO8945	Grevillea robusta	Species	Proteaceae	Eukaryota	leaves	n.a.	n.a.	PMID[17243726]
NPO18618	Neurolaena lobata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO18618	Neurolaena lobata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24476550]
NPO40970	Nostoc sp. GSV 224	Strain	Nostocaceae	Bacteria	n.a.	n.a.	n.a.	PMID[9090872]
NPO9705	Meyerozyma guilliermondii	Species	Debaryomycetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8945	Grevillea robusta	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8305	Katsuwonus pelamis	Species	Scombridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18618	Neurolaena lobata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4198	Ungernia vvedenskyi	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7240	Osteospermum oppositifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1969	Streptomyces pilosus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO834	Peperomia clusiifolia	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7788	Rana catesbeiana	Species	Ranidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12744	Ajuga nipponensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19541	Smilax moranensis	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8623	Anneissia japonica	Species	Comatulidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8426	Tinospora rumphii	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4541	Capnella lacertiliensis	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1537	Vaccinium arctostaphylos	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23436	Cladrastis sikokiana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO40970	Nostoc sp. GSV 224	Strain	Nostocaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8811	Cytisus prolifer	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28833	Eleutherococcus sieboldianus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3613	Eriobotrya deflexa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10879	Lasius meridionalis	Species	Formicidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19804	Lycopodium saururus	Species	Lycopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8305	Katsuwonus pelamis	Species	Scombridae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO8945	Grevillea robusta	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8945	Grevillea robusta	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3613	Eriobotrya deflexa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12744	Ajuga nipponensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8945	Grevillea robusta	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8811	Cytisus prolifer	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1969	Streptomyces pilosus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO28833	Eleutherococcus sieboldianus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19804	Lycopodium saururus	Species	Lycopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5335	Nostoc sp	Species	Nostocaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO834	Peperomia clusiifolia	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8623	Anneissia japonica	Species	Comatulidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18618	Neurolaena lobata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7788	Rana catesbeiana	Species	Ranidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9705	Meyerozyma guilliermondii	Species	Debaryomycetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4541	Capnella lacertiliensis	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3613	Eriobotrya deflexa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19541	Smilax moranensis	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8305	Katsuwonus pelamis	Species	Scombridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8426	Tinospora rumphii	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1537	Vaccinium arctostaphylos	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7240	Osteospermum oppositifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10879	Lasius meridionalis	Species	Formicidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4198	Ungernia vvedenskyi	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12744	Ajuga nipponensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23436	Cladrastis sikokiana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8945	Grevillea robusta	Species	Proteaceae	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	3

Activity Type	# Activity
Cell line	3

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
NPT114	Cell line	LoVo	Homo sapiens	IC50	=	100.0	nM	PMID[9090872]
NPT91	Cell line	KB	Homo sapiens	IC50	=	100.0	nM	PMID[9090872]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	=	100.0	nM	PMID[9090872]

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 NPC49315 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	14428
0.1-0.2	33723
0.2-0.3	1681
0.3-0.4	11
0.4-0.5	1
0.5-0.6	2
0.6-0.7	3
0.7-0.8	1
0.8-0.85	0
0.85-0.9	3
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8977	High Similarity	NPC482601
0.8977	High Similarity	NPC151030
0.8506	High Similarity	NPC132771
0.7368	Intermediate Similarity	NPC269383
0.7143	Intermediate Similarity	NPC271958
0.7143	Intermediate Similarity	NPC45112
0.7143	Intermediate Similarity	NPC263507
0.7143	Intermediate Similarity	NPC482624
0.7143	Intermediate Similarity	NPC482625
0.6701	Remote Similarity	NPC207675
0.67	Remote Similarity	NPC86678
0.6	Remote Similarity	NPC134413
0.5577	Remote Similarity	NPC212699
0.5225	Remote Similarity	NPC227778

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC49315 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2392
0.1-0.2	6386
0.2-0.3	369
0.3-0.4	1
0.4-0.5	0
0.5-0.6	1
0.6-0.7	0
0.7-0.8	1
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
0.7143	Intermediate Similarity	NPD7959	Clinical (unspecified phase)
0.5849	Remote Similarity	NPD8014	Clinical (unspecified phase)

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